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Virchows Archiv : An International... Jan 2022Papillary lesions of the breast represent a heterogeneous group of lesions including benign papillomas, papillomas with focal epithelial atypia, fully fledged ductal... (Review)
Review
Papillary lesions of the breast represent a heterogeneous group of lesions including benign papillomas, papillomas with focal epithelial atypia, fully fledged ductal carcinoma in situ (DCIS) or lobular neoplasia, papillary DCIS, encapsulated papillary carcinomas without or with invasion, solid papillary carcinomas, and invasive papillary carcinomas. A micropapillary pattern characterized by lack of fibrous stalks within the papillae is observed in micropapillary DCIS and invasive micropapillary carcinoma. In addition, a variety of other rare breast lesions reveals a papillary architecture such as tall cell carcinoma with reversed polarity (TCCRP) and mucinous cystadenocarcinoma, adenomyoepithelioma, and secretory carcinoma. In addition, benign lesions such as usual ductal hyperplasia, apocrine metaplasia, gynecomastia, and juvenile papillomatosis may show a papillary or micropapillary architecture. Fragments of a benign papilloma in a breast biopsy are considered a lesion of uncertain malignant potential (B3 in the European classification) and excision is mostly recommended. Although the knowledge about molecular pathology of papillary breast lesions has increased, there is not sufficient evidence for diagnostically useful molecular features, yet. The aim of this review is to provide an update on papillary and micropapillary lesions with emphasis on problematic areas for daily diagnostic work including biopsies.
Topics: Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Humans; Male; Papilloma
PubMed: 34734332
DOI: 10.1007/s00428-021-03182-7 -
Computational and Structural... 2021Gliomas are one of the most common types of primary tumors in central nervous system. Previous studies have found that macrophages actively participate in tumor growth.
BACKGROUND
Gliomas are one of the most common types of primary tumors in central nervous system. Previous studies have found that macrophages actively participate in tumor growth.
METHODS
Weighted gene co-expression network analysis was used to identify meaningful macrophage-related gene genes for clustering. Pamr, SVM, and neural network were applied for validating clustering results. Somatic mutation and methylation were used for defining the features of identified clusters. Differentially expressed genes (DEGs) between the stratified groups after performing elastic regression and principal component analyses were used for the construction of MScores. The expression of macrophage-specific genes were evaluated in tumor microenvironment based on single cell sequencing analysis. A total of 2365 samples from 15 glioma datasets and 5842 pan-cancer samples were used for external validation of MScore.
RESULTS
Macrophages were identified to be negatively associated with the survival of glioma patients. Twenty-six macrophage-specific DEGs obtained by elastic regression and PCA were highly expressed in macrophages at single-cell level. The prognostic value of MScores in glioma was validated by the active proinflammatory and metabolic profile of infiltrating microenvironment and response to immunotherapies of samples with this signature. MScores managed to stratify patient survival probabilities in 15 external glioma datasets and pan-cancer datasets, which predicted worse survival outcome. Sequencing data and immunohistochemistry of Xiangya glioma cohort confirmed the prognostic value of MScores. A prognostic model based on MScores demonstrated high accuracy rate.
CONCLUSION
Our findings strongly support a modulatory role of macrophages, especially M2 macrophages in glioma progression and warrants further experimental studies.
PubMed: 34471502
DOI: 10.1016/j.csbj.2021.08.019 -
Computational and Structural... 2022Shc SH2-domain binding protein 1 (SHCBP1), a protein specific binding to SH2 domain of Src homolog and collagen homolog (Shc), takes part in the regulation of various...
Shc SH2-domain binding protein 1 (SHCBP1), a protein specific binding to SH2 domain of Src homolog and collagen homolog (Shc), takes part in the regulation of various signal transduction pathways, which has been reported to be associated with tumorigenesis and progression. However, the pathological mechanisms are not completely investigated. Thus, this study aimed to comprehensively elucidate the potential functions of SHCBP1 in multiple cancer types. The comprehensive analyses for SHCBP1 in various tumors, including gene expression, diagnosis, prognosis, immune-related features, genetic alteration, and function enrichment, were conducted based on multiple databases and analysis tools. SHCBP1 was upregulated in most types of cancers. The results of qRT-PCR had confirmed that SHCBP1 mRNA was significantly upregulated in lung adenocarcinoma (LUAD) and liver hepatocellular carcinoma (LIHC) cell lines. Based on the receiver operating characteristic (ROC) and survival analysis, SHCBP1 was considered as a potential diagnostic and prognostic biomarker. Furthermore, SHCBP1 expression was linked with tumor immunity and immunosuppressive microenvironment according to the correlation analysis of SHCBP1 expression with immune cells infiltration, immune checkpoint genes, and immune-related genes (MHC genes, chemokines, and chemokines receptors). Moreover, SHCBP1 expression correlated with tumor mutational burden (TMB), microsatellite instability (MSI), and neoantigens. The feature of SHCBP1 mutational landscape in pan-cancer was identified. Finally, we focused on investigating the clinical significance and the potential biological role of SHCBP1 in LUAD. Our study comprehensively uncovered that SHCBP1 could be identified as an immune-related biomarker for cancer diagnosis and prognosis, and a potential therapeutic target for tumor immunotherapy.
PubMed: 35782736
DOI: 10.1016/j.csbj.2022.06.039 -
International Journal of Gynecological... Sep 2023Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly...
Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade serous carcinoma diagnosis and treatment, a panel of experts convened for a workshop in October 2022 to develop a consensus document addressing pathology, translational research, epidemiology and risk, clinical management, and ongoing research. In addition, the patient perspective was discussed. The recommendations developed by this expert panel-presented in this consensus document-will guide practitioners in all settings regarding the clinical management of women with low-grade serous carcinoma and discuss future opportunities to improve research and patient care.
Topics: Humans; Female; Consensus; Quality of Life; Peritoneal Neoplasms; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Ovarian Neoplasms
PubMed: 37591609
DOI: 10.1136/ijgc-2023-004610 -
Computational and Structural... 2023Endothelial cells (ECs) play an important role in tumor progression. Currently, the main target of anti-angiogenic therapy is the vascular endothelial growth factor...
Endothelial cells (ECs) play an important role in tumor progression. Currently, the main target of anti-angiogenic therapy is the vascular endothelial growth factor (VEGF) pathway. Some patients do benefit from anti-VEGF/VEGFR therapy; however, a large number of patients do not have response or acquire drug resistance after treatment. Moreover, anti-VEGF/VEGFR therapy may lead to nephrotoxicity and cardiovascular-related side effects due to its action on normal ECs. Therefore, it is necessary to identify targets that are specific to tumor ECs and could be applied to various cancer types. We integrated single-cell RNA sequencing data from six cancer types and constructed a multi-cancer EC atlas to decode the characteristic of tumor ECs. We found that tip-like ECs mainly exist in tumor tissues but barely exist in normal tissues. Tip-like ECs are involved in the promotion of tumor angiogenesis and inhibition on anti-tumor immune responses. Moreover, tumor cells, myeloid cells, and pericytes are the main sources of pro-angiogenic factors. High proportion of tip-like ECs is associated with poor prognosis in multiple cancer types. We also identified that prostate-specific membrane antigen (PSMA) is a specific marker for tip-like ECs in all the cancer types we studied. In summary, we demonstrate that tip-like ECs are the main differential EC subcluster between tumors and normal tissues. Tip-like ECs may promote tumor progression through promoting angiogenesis while inhibiting anti-tumor immune responses. PSMA was a specific marker for tip-like ECs, which could be used as a potential target for the diagnosis and treatment of non-prostate cancers.
PubMed: 36659929
DOI: 10.1016/j.csbj.2022.12.049 -
Archives of Pathology & Laboratory... Jan 2023Mucinous lesions of the breast encompass many entities ranging from benign to malignant and nonneoplastic to neoplastic. Lesions discussed under this category are... (Review)
Review
CONTEXT.—
Mucinous lesions of the breast encompass many entities ranging from benign to malignant and nonneoplastic to neoplastic. Lesions discussed under this category are mucocele-like lesion, mucinous carcinoma, mucinous micropapillary carcinoma, solid papillary carcinoma, mucinous cystadenocarcinoma, mucoepidermoid carcinoma, invasive lobular carcinoma with extracellular mucin, mucinous ductal carcinoma in situ, and metastasis.
OBJECTIVE.—
To review clinical, pathologic, and molecular features of mucinous lesions of the breast, their differential diagnoses, and challenging features on core needle biopsies.
DATA SOURCES.—
The existing scientific and clinical literature as of December 2021.
CONCLUSIONS.—
The category of mucinous lesions of the breast is vast and the differential diagnosis can be challenging, especially on core needle biopsies. In all cases, clinical, radiologic, and pathologic correlation is necessary to reach a comprehensive diagnosis. Given that the prognosis and management of each entity is different, being aware of these entities and their nuances is critical for a pathologist to guide accurate management.
Topics: Female; Humans; Adenocarcinoma, Mucinous; Biopsy, Large-Core Needle; Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating
PubMed: 36577093
DOI: 10.5858/arpa.2022-0054-RA -
Autopsy & Case Reports 2022Papillary cystadenocarcinoma of the salivary gland is a very rare malignant neoplasm accounting for only 2% of all salivary gland lesions. In 1991 it was first included... (Review)
Review
Papillary cystadenocarcinoma of the salivary gland is a very rare malignant neoplasm accounting for only 2% of all salivary gland lesions. In 1991 it was first included as a separate entity in the World Health Organization (WHO) classification of salivary gland tumors and in 2017 WHO Classification, the tumor was clubbed as a sub-variant of adenocarcinoma, not otherwise specified. It most commonly occurs in the major salivary glands. Herein we report a case of salivary papillary cystadenocarcinoma in a 54-year-old female, who presented with rapid enlargement of the right parotid swelling. Based on radiology and fine-needle aspiration cytology, a working diagnosis of the malignant tumor involving the superficial lobe of the right parotid gland was made. In view of the malignant nature of the swelling, superficial parotidectomy was done. The histopathology and immunohistochemistry of the mass confirmed the diagnosis of papillary cystadenocarcinoma of the right parotid. With the revised 2017 WHO classification of salivary gland tumors, it is important to report all rare subtypes in order to understand their biology and behavior.
PubMed: 35252049
DOI: 10.4322/acr.2021.357 -
Genome Medicine May 2020Distinct prevalence of inherited genetic predisposition may partially explain the difference of cancer risks across ancestries. Ancestry-specific analyses of germline...
BACKGROUND
Distinct prevalence of inherited genetic predisposition may partially explain the difference of cancer risks across ancestries. Ancestry-specific analyses of germline genomes are required to inform cancer genetic risk and prognosis of diverse populations.
METHODS
We conducted analyses using germline and somatic sequencing data generated by The Cancer Genome Atlas. Collapsing pathogenic and likely pathogenic variants to cancer predisposition genes (CPG), we analyzed the association between CPGs and cancer types within ancestral groups. We also identified the predisposition-associated two-hit events and gene expression effects in tumors.
RESULTS
Genetic ancestry analysis classified the cohort of 9899 cancer cases into individuals of primarily European (N = 8184, 82.7%), African (N = 966, 9.8%), East Asian (N = 649, 6.6%), South Asian (N = 48, 0.5%), Native/Latin American (N = 41, 0.4%), and admixed (N = 11, 0.1%) ancestries. In the African ancestry, we discovered a potentially novel association of BRCA2 in lung squamous cell carcinoma (OR = 41.4 [95% CI, 6.1-275.6]; FDR = 0.002) previously identified in Europeans, along with a known association of BRCA2 in ovarian serous cystadenocarcinoma (OR = 8.5 [95% CI, 1.5-47.4]; FDR = 0.045). In the East Asian ancestry, we discovered one previously known association of BRIP1 in stomach adenocarcinoma (OR = 12.8 [95% CI, 1.8-90.8]; FDR = 0.038). Rare variant burden analysis further identified 7 suggestive associations in African ancestry individuals previously described in European ancestry, including SDHB in pheochromocytoma and paraganglioma, ATM in prostate adenocarcinoma, VHL in kidney renal clear cell carcinoma, FH in kidney renal papillary cell carcinoma, and PTEN in uterine corpus endometrial carcinoma. Most predisposing variants were found exclusively in one ancestry in the TCGA and gnomAD datasets. Loss of heterozygosity was identified for 7 out of the 15 African ancestry carriers of predisposing variants. Further, tumors from the SDHB or BRCA2 carriers showed simultaneous allelic-specific expression and low gene expression of their respective affected genes, and FH splice-site variant carriers showed mis-splicing of FH.
CONCLUSIONS
While several CPGs are shared across patients, many pathogenic variants are found to be ancestry-specific and trigger somatic effects. Studies using larger cohorts of diverse ancestries are required to pinpoint ancestry-specific genetic predisposition and inform genetic screening strategies.
Topics: Ataxia Telangiectasia Mutated Proteins; BRCA2 Protein; Fanconi Anemia Complementation Group Proteins; Female; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Male; Neoplasms; RNA Helicases; Risk Factors; Succinate Dehydrogenase; Von Hippel-Lindau Tumor Suppressor Protein
PubMed: 32471518
DOI: 10.1186/s13073-020-00744-3 -
Computational and Structural... 2022The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein...
The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein with biological functions such as promoting cell growth, migration, aggregation, metastasis and adhesion, and plays an important role in cancers and coronavirus disease 2019 (COVID-19). Unlike angiotensin-converting enzyme 2 (ACE2), AXL was highly expressed in respiratory system cells. In this study, we verified the AXL expression in cancer and normal tissues and found AXL expression was strongly correlated with cancer prognosis, tumor mutation burden (TMB), the microsatellite instability (MSI) in most tumor types. Immune infiltration analysis also demonstrated that there was an inextricable link between AXL expression and immune scores in cancer patients, especially in BLCA, BRCA and CESC. The NK-cells, plasmacytoid dendritic cells, myeloid dendritic cells, as one of the important components of the tumor microenvironment, were highly expressed AXL. In addition, AXL-related tumor neoantigens were identified and might provide the novel potential targets for tumor vaccines or SARS-Cov-2 vaccines research in cancer patients.
PubMed: 35782741
DOI: 10.1016/j.csbj.2022.06.051 -
Human Pathology Jun 2021With major advancements and frequent use of abdominal imaging techniques, hepatic cysts are increasingly encountered in clinical practice. Although the majority of cysts... (Review)
Review
With major advancements and frequent use of abdominal imaging techniques, hepatic cysts are increasingly encountered in clinical practice. Although the majority of cysts are benign, a small subset represents neoplastic precursors to cholangiocarcinoma. These cystic precursors include intraductal papillary neoplasms of the bile duct (IPNB) and mucinous cystic neoplasms of the liver (MCN-L), and bear striking pathologic resemblance to corresponding cystic neoplastic precursors within the pancreas. This review examines the salient clinical, gross, microscopic and molecular features of IPNBs and MCN-Ls, and, in particular, provides histopathologic comparison to their pancreatic counterparts. Considering these neoplasms may be diagnostically challenging, we also discuss other hepatic lesions within the differential diagnosis, and the potential for molecular methods to improve their preoperative evaluation and the early detection of cholangiocarcinoma.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Cystadenocarcinoma, Mucinous; Diagnosis, Differential; Humans; Liver Neoplasms
PubMed: 33383041
DOI: 10.1016/j.humpath.2020.12.010