Experience Sharing in Pathological Diagnosis of Early Adenocarcinoma of the Lung.

Background: In daily work, there are still many pathologists who have difficulty handling the diagnosis of atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic adenocarcinoma, and the boundaries are not clear enough. Sometimes, the diagnosis is difficult, and there is sometimes poor reproducibility between different pathologists. Accurate diagnosis and differential diagnosis require a certain amount of experience. Methods: During the COVID-19 pandemic, we collected a large number (n = 381) of specimens of early lung adenocarcinoma, most of which (n = 356) were solitary lesions and 25 were multifocal lesions. There were 78 nodules in multifocal lesions, total 434 nodules. We summarized very careful microscopic observation and comparative analysis on all frozen and paraffin sections collected from many early lung adenocarcinoma specimens, continuously summarizing our experience. Results: Based on the World Health Organization's 2021 classification and diagnostic criteria for lung adenocarcinoma, new perspectives have been proposed on how to distinguish between atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic adenocarcinoma. In particular, new perspectives have been proposed on how to identify invasive aspects, and there are also some new perspectives on early lung mucinous lesions. Conclusion: Atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic adenocarcinoma all have corresponding morphological diagnostic criteria, but the morphological boundaries are sometimes not easy to determine and require some experience accumulation. The intraoperative frozen pathological diagnosis of early adenocarcinoma of the lung needs to be closely combined with imaging examination, and has very rich morphological experience.

SERPINE1 and SERPINB7 as potential biomarkers for intravenous vitamin C treatment in non-small-cell lung cancer.

High dose intravenous vitamin C (IVC) has been proposed as a pro-oxidant anticancer agent. However, there is a lack of biomarkers that are specific for this treatment. Here, we explored profiles of gene expression responding to IVC treatment in non-small cell lung cancer (NSCLC) cells as an effort for potential biomarker discovery. Genome-wide RNA-seq was performed in human NSCLC cell lines treated with pharmacological concentrations of vitamin C(VitC) for differential expression of genes. The identified genes were analyzed for correlations with patient prognosis using data from the Kaplan-Meier Plotter and the Human Protein Atlas databases. Further, tumor samples from a retrospective study of 153 NSCLC patients were analyzed with immunohistochemistry for expression of targeted genes, and patient prognosis was correlated to these genes. Two genes, namely SERPINE1 and SERPINB7 were found to be downregulated in NSCLC cells following VitC treatment. Combined patient data from the cohort analysis and online databases revealed that these 2 genes presented an unfavorable prognostic prediction of overall survival (OS) in NSCLC patients receiving standard of care. However, high expression level of these 2 genes were associated with prolonged OS in NSCLC patients receiving IVC in addition to standard of care. These data revealed that SERPINE1 and SERPINB7 have the potential to serve as predictive factors indicating favorable responses to IVC treatment in patients with NSCLC. Further validations are warranted.

Insight into the Molecular Mechanism of Flower Color Regulation in Rhododendron latoucheae Franch: A Multi-Omics Approach.

Rhododendron latoucheae Franch. (R. latoucheae) is a valuable woody plant known for its high ornamental value. While purple flowers are a distinct and attractive variant phenotype of R. latoucheae, the underlying mechanism regulating its flower color is still poorly understood. To investigate the molecular regulatory mechanism responsible for the variation in flower color, we selected plants with white-pink and purple petals as the object and conducted analyses of metabolites, key genes, and transcription factors associated with flower color. A combined metabolome-transcriptome analysis was performed, and the expression of key genes was subsequently verified through qRT-PCR experiments. The results of our study demonstrated a significant enrichment of differential metabolites in the flavonoid metabolic pathway. Changes in anthocyanin content followed the same trend as the observed flower color variations, specifically showing significant correlations with the contents of malvidin-3-O-glucoside, dihydromyricetin, gallocatechin, and peonidin-3-O-glucoside. Furthermore, we identified three key structural genes (F3GT1, LAR, ANR) and four transcription factors (bHLH130, bHLH41, bHLH123, MYB4) that are potentially associated with the biosynthesis of flavonoid compounds, thereby influencing the appearance of purple flower color in R. latoucheae.

Effects of landscape conservation on the ecohydrological and water quality functions and services and their driving factors.

Since the implementation of landscape conservation of the green heart area in the Changsha-Zhuzhou-Xiangtan Metropolitan Region, the landscape structure and pattern have changed significantly. The ecosystem service functions in the area have been improved, but the status of ecohydrological and water quality and service functions (EHWQSFs) is still unclear. To clarify the status of EHWQSFs and their driving factors influenced by landscape conservation, this study analysed landscape changes using remote sensing image data from 1998, 2008, and 2018 and the changes and their spatial characteristics using the Soil and Water Assessment Tool (SWAT) and spatial analysis methods. The results showed that the dominant land types in the area were forestland and cropland from 1998 to 2018; the area of forestland and construction land expanded and that of cropland decreased year by year; the annual average surface runoff volume rose, and the annual average actual evapotranspiration and soil water content fell from 1998 to 2008 and rose from 2008 to 2018; and all pollutant indicators decreased significantly after 2008. The areas with higher surface runoff were mainly concentrated in the central and southern regions, those with higher evapotranspiration were in the northwestern and southwestern regions, those with higher soil water content were in the northern region, and those with higher sediment and nitrogen and phosphorus pollutant contents were in the central and southeastern regions. The results showed that land use, land cover and meteorological factors were the most significant drivers on EHWQSFs and illustrated that EHWQSFs in the area decreased after 1998. There was a significant improvement after 2008 and the area currently has a good status. This study not only provides insights into land use, land cover and meteorological factors that have significant impacts on EHWQSFs but also highlights that the landscape conservation of the area can improve ecosystem service functions.

Malignant transformation of craniopharyngioma with detailed follow-up.

A 29-year-old male patient was admitted into hospital with the main complaint of progressive visual disturbance. Both CT SCAN and MRI demonstrated a cystic-solid contrast-enhancing sellar-suprasellar mass with obvious calcification. Histopathological examination of the first resected specimen showed a typical appearance of adamantinomatous craniopharyngioma. The patient received gamma knife therapy after his first operation because of partial tumor removal. He experienced two relapses in the subsequent 2 years, for which only surgical resection was performed. The later histopathology presented malignant appearance with tumor cells moderate to severe pleomorphism, hyperchromasia, increased nuclear cytoplastic ratio, high mitotic activity (30/10 high power fields) and focal coagulative necrosis. The patient died 9 months after identification of histologic malignancy. Clinical and histopathological features, biological behavior of one case of malignant craniopharyngioma were discussed, with a brief review of the relevant literature.

Traumatic breast transposal to the abdominal wall: A case report.

Although abdominal wall masses are commonly observed in clinical practice, traumatic breast transposal appearing as an abdominal wall mass is a rare event. The unique phenomenon of a post-traumatic breast growing healthily in the abdominal wall has never previously been reported. The current study presents the case of a 40-year-old female who developed an unusually transposed, but healthy mammary gland in the right upper abdominal wall following a severe pedestrian traffic accident. In that accident, the powerful impact of the car caused multiple right-sided rib fractures, lung injuries and a protruding mass on the right abdominal wall. This sudden onset protruding mass was indicated to be breast tissue by computed tomography imaging and ultrasound scanning. The transposed mammary gland was resected and a pathological examination confirmed that it consisted of normal breast tissue. In this case, the force of the car caused no significant damage or necrosis to the right breast, but instead was sufficient to shift the mammary gland to the abdomen, where it grew healthily 6 months in its new location. This case highlights the capability of the mammary gland to withstand a powerful impact and survive. Moreover, it advances our knowledge of how mammary tissues respond to severe blunt-force impacts.

[Pulmonary epithelioid hemangioendothelioma: a clinicopathological analysis].

OBJECTIVE: To report 3 cases of pulmonary epithelioid haemangioendothelioma (PEH) and therefore to improve the understanding of this tumor. METHODS: The clinical pathological features of 3 cases of PEH were described and related literatures were reviewed. RESULTS: The etiology of this rare disease remained unknown. Symptoms were scanty and usually mild. Chest radiograph or computed tomography usually revealed multiple bilateral pulmonary nodules. Histologically, crown-like clusters of epithelioid tumor cells or spindle cells were filled in the alveoli at the periphery of the tumor nodules, while the central part of the nodules contained myxoid to hyaline matrix. Tumor cells generally lacked pleomorphism, mitotic activity and necrosis. They were immunohistochemically positive for CD(31) and CD(34). CK staining was positive in some cases. There was no effective treatment for this disease and its prognosis was unpredictable. CONCLUSIONS: PEH is a low grade malignancy and represents a distinct clinical pathological entity. It is rare and often misdiagnosed as other pulmonary diseases.

[Pleuropulmonary blastoma of adults: a clinicopathological analysis].

OBJECTIVE: To report two cases of pleuropulmonary blastoma (PPB) of adults and improving the understanding of this tumor. METHODS: The clinicopathological features of two cases of adult PPB were examined by light microscope and an immunohistochemical study. RESULTS: As a rare malignant mesenchymal tumor, PPB arose from primitive cells of lung, pleura and mediastinum. Consisting of primitive undifferentiated sarcoma cells and few epithelial cells, the tumor was positive for mesenchymal differentiated markers by immunohistochemistry. CONCLUSION: PPB is a rare malignant embryonal tumor. The diagnosis of this tumor is rather difficult since it lacks pathomorphological or immunohistochemical features.

Serum proteome analysis for profiling protein markers associated with carcinogenesis and lymph node metastasis in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC), one of the most common cancers in population with Chinese or Asian progeny, poses a serious health problem for southern China. It is unfortunate that most NPC victims have had lymph node metastasis (LNM) when first diagnosed. We believe that the 2D based serum proteome analysis can be useful in discovering new biomarkers that may aid in the diagnosis and therapy of NPC patients. To filter the tumor specific antigen markers of NPC, sera from 42 healthy volunteers, 27 non-LNM NPC patients and 37 LNM NPC patients were selected for screening study using 2D combined with MS. Pretreatment strategy, including sonication, albumin and immunoglobulin G (IgG) depletion, was adopted for screening differentially expressed proteins of low abundance in serum. By 2D image analysis and MALDI-TOF-MS identification, twenty-three protein spots were differentially expressed. Three of them were further validated in the sera using enzyme-linked immunosorbent assay (ELISA). Our research demonstrates that HSP70, sICAM-1 and SAA, confirmed with ELISA at sera and immunohistochemistry, are potential NPC metastasis-specific serum biomarkers which may be of great underlying significance in clinical detection and management of NPC.

[Comparative proteomics of the serum in patients with nasopharyngeal carcinoma: a study with two-dimensional electrophoresis and MALDI-TOF-MS].

OBJECTIVE: To screen the tumor specific antigens of nasopharyngeal carcinoma (NPC) in the serum of the patients. METHODS: Two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was employed to screen the specific biomarkers of NPC in the sera from 42 healthy volunteers, 37 NPC patients with lymph node metastasis and 27 NPC patients without lymphatic metastasis. RESULTS: After pretreatment including albumin and immunoglobulin (IgG) depletion and desalting, the sera were subjected to 2-DE and image analysis. The differentially expressed protein spots were identified by MALDI-TOF-MS. Sera pretreatment resulted in better repeatability and resolution on the reference gel because of albumin and IgG depletion. From optimized 2-DE gel images, 29 spots indicating differential protein expression were identified by MALDI-TOF-MS to represent 23 proteins. Transferrin, ZNF544 protein, transthyretin, FAD-synthetase and NM23-H1 proteins were down-regulated and 12-lipoxygenase, serum amyloid A1 protein precursor, cytochrome P450, sICAM-1, cathepsin G and lysine-specific histone demethylase 1 were upregulated in the two groups of NPC patients as compared with the healthy group. Increased expressions of 12-lipoxygenase, sICAM-1, cathepsin G and lysine-specific histone demethylase 1 were detected in NPC patients with lymph node metastasis as compared with the patients without lymph node metastasis, but heat shock protein 70 was expressed only in NPC patients with lymph node metastasis. CONCLUSION: The 2-DE-based serum proteome analysis can be useful in detecting the protein expression alterations due to carcinogenesis and development of NPC, and the newly discovered biomarkers might help in the diagnosis of NPC.

[Clinical and pathologic features of malignant myoepithelioma of salivary glands].

OBJECTIVE: To analyze the clinical features, morphology and biologic behavior of primary malignant myoepithelioma (MME) of salivary glands. METHODS: The H&E sections of 16 MME cases were reviewed. Immunohistochemical study using EnVision method for cytokeratin (CK), epithelial membrane antigen (EMA), vimentin, S-100 protein, desmin, muscle-specific actin (MSA), smooth muscle actin (SMA), Myo, proliferation cell nuclear antigen (PCNA), leukocyte common antigen (LCA) and glial fibrillary acidic protein (GFAP) was carried out. RESULTS: Of the 16 patients studied, 6 were males and 10 were females. Their ages ranged from 12 to 65 years (with an average age of 44 years). The tumor occurred predominantly in the parotid gland and minor salivary gland of the palate. Common clinical features included sudden and rapid tumor growth, superficial ulceration, bony destruction and nerve infiltration. Seven of the 16 patients developed local recurrences, while 2 patients had metastasis in the lymph nodes of submandibular or other cervical regions. Most tumors infiltrated adjacent normal salivary gland, adipose, muscular and bony tissues. The extent of local invasion however varied. Histologically, MME showed a wide range of morphologic appearance, with various combinations of clear, spindle, epithelioid or plasmacytoid cells. The tumor cells were atypical and demonstrated high mitotic activity. In this study, 9 cases were composed predominantly of clear tumor cells. Immunohistochemically the tumor cells were positive for CK, EMA, MSA, desmin and S-100 protein. CONCLUSIONS: In general, MME is a rare and low-grade malignant salivary gland tumor. It carries a low potential for lymph node or distant metastasis but relatively high tendency for local recurrences, resulting in destruction of adjacent soft and bony tissues. The biologic behavior also varies, depending on the site of involvement. Morphologic diagnosis of MME can be difficult in view of the wide spectrum of histologic changes. A definitive diagnosis however is possible with the application of immunohistochemistry.

[Comparison of TPS, CEA, CYFRA21-1 and STNFR in diagnosis of lung cancer].

BACKGROUND: In recent years, new progress has been made in research of tumor markers. And namely tissue polypeptide specific antigen (TPS), cytokeratin 19-fragments (CYFRA21-1) and soluble tumor necrosis factor receptor (STNFR) are new tumor markers that have been used in clinical application. The aim of this study is to determine and compare the diagnostic value of 4 kinds of tumor markers, TPS, carcinoembryonic antigen (CEA), CYFRA21-1 and STNFR in patients with lung cancer. METHODS: The serum levels of TPS, CEA, CYFRA21-1 and STNFR were determined in 72 patients with lung cancer, 54 patients with pulmonary benign diseases and 32 healthy adults by enzyme-linked immunosorbent assay (ELISA). RESULTS: The levels of the four tumor markers in lung cancer group were significantly higher than those in benign disease group (P < 0.005) and healthy control group (P < 0.001). Among the four markers, STNFR had the highest sensitivity (81.9%), CYFRA21-1 had the highest specificity (91.5%) and TPS had the highest accuracy (83.5%). CONCLUSIONS: TPS, CYFRA21-1 and STNFR can be used as very useful and sensitive tumor markers in the diagnosis of lung cancer, in which CYFRA21-1 may be the most useful tumor marker for clinical application.