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American Journal of Clinical Pathology Jun 2022Metastatic neoplasms involving the stomach are rare and diagnostically challenging if clinical history of malignancy is absent or unavailable. This study was designed to...
OBJECTIVES
Metastatic neoplasms involving the stomach are rare and diagnostically challenging if clinical history of malignancy is absent or unavailable. This study was designed to identify the tumors that most frequently metastasize to the stomach and the morphologic features that can provide clues to investigate the possibility of metastasis and predict the primary sites.
METHODS
All patients with metastatic neoplasms involving the stomach were included in the study. The H&E- and immunohistochemical-stained slides were reviewed, and all clinical, endoscopic, and radiologic information was recorded.
RESULTS
One hundred fifty patients, including 84 (56%) women and 66 (44%) men (mean age, 64 years), were identified. Gastric metastases were the initial presentation in 15% cases. Epithelial tumors (73.3%) comprised the largest group, followed by melanoma (20.6%), sarcomas (4%), germ cell tumors (1.3%), and hematolymphoid neoplasms (0.7%). Lobular breast carcinoma was the most common neoplasm overall in women, while in men, it was melanoma. Solid/diffuse growth pattern (75%) was more common compared with glandular morphology. The solid/diffuse category included lobular breast carcinoma (21.3%), melanoma (20.6%), and renal cell carcinoma (10.6%), while the glandular category was dominated by gynecologic serous carcinomas (7.3%) with papillary/micropapillary architecture.
CONCLUSIONS
Metastatic neoplasms should be considered in the differential diagnosis of gastric neoplasms, particularly those with a diffuse/solid growth pattern. Glandular neoplasms are difficult to differentiate from gastric primaries except for Müllerian neoplasms, which frequently show a papillary/micropapillary architecture.
Topics: Breast Neoplasms; Carcinoma, Lobular; Cystadenocarcinoma, Serous; Female; Humans; Kidney Neoplasms; Male; Melanoma; Middle Aged; Ovarian Neoplasms; Stomach; Stomach Neoplasms
PubMed: 34875001
DOI: 10.1093/ajcp/aqab202 -
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 -
Modern Pathology : An Official Journal... Jan 2016Serous carcinoma (SC) represents ~10% of endometrial carcinomas, but is responsible for almost 40% of cancer deaths. This article reviews the main pathological features,... (Review)
Review
Serous carcinoma (SC) represents ~10% of endometrial carcinomas, but is responsible for almost 40% of cancer deaths. This article reviews the main pathological features, differential diagnosis, and the usefulness of molecular pathology and immunohistochemistry in its diagnosis. Most helpful features for the diagnosis include: irregularly shaped and sized papillae, slit-like spaces, cell stratification and budding, highly atypical cells, architectural and cytological discordance in pseudoglandular tumors, as well as lack of endometrioid features. SC shows typically a predominant papillary growth, which is also found in some subtypes of endometrioid carcinoma of the endometrium (EEC). Distinction is easy when attention is paid to the presence of diffuse marked nuclear pleomorphism, but also to the complex papillary architecture. SC may also show a solid or pseudoglandular patterns, and in these cases differential diagnosis may be difficult with EEC grade 3. Moreover, a high proportion of SC may exhibit clear cells, and, thus, may be confused with clear cell carcinoma. Finally, it is sometimes difficult to distinguish mixed SC-EEC, from SC that combines papillary and pseudoglandular growths. Although there is not a single immunohistochemical marker for distinguishing SC from its mimickers, some antibodies are useful (p53, p16, IMP2, and IMP3), particularly when used in combination. Diagnosis of SC may be even more problematic in small biopsies; a diagnosis of high-grade endometrial carcinoma, SC component can not be excluded, is acceptable as a managerial approach, so it could be taken into account at the time of final surgery.
Topics: Cystadenocarcinoma, Serous; Endometrial Neoplasms; Female; Humans
PubMed: 26715173
DOI: 10.1038/modpathol.2015.141 -
Surgical Oncology Clinics of North... Apr 2016Management of cystic neoplasms of the pancreas is challenging as it relies on radiologic and cyst fluid markers to discriminate between benign and pre-cancerous lesions,... (Review)
Review
Management of cystic neoplasms of the pancreas is challenging as it relies on radiologic and cyst fluid markers to discriminate between benign and pre-cancerous lesions, however their ability to predict malignancy is limited. While asymptomatic serous cystadenomas can be managed conservatively, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are more difficult to manage. A selective approach, based on the preoperative likelihood of high-grade dysplasia or invasive disease, is the standard of care. Research is focusing on the development of pre-operative markers for identifying high risk lesions, which will spare patients with low-risk or benign lesions the risks of pancreatectomy.
Topics: Cystadenocarcinoma, Mucinous; Cystadenoma, Mucinous; Cystadenoma, Serous; Humans; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 27013369
DOI: 10.1016/j.soc.2015.11.006 -
Journal of Obstetrics and Gynaecology :... Jul 2022The aim of this retrospective population-based study was to investigate the survival outcomes and prognostic factors of patients with the two cervical carcinomas. A...
The aim of this retrospective population-based study was to investigate the survival outcomes and prognostic factors of patients with the two cervical carcinomas. A cohort of patients diagnosed with papillary serous adenocarcinoma of the uterine cervix (PSAC) and papillary squamous cell carcinoma (PSCC) between 1973 and 2015 were drawn from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method, and prognostic factors were assessed using Cox proportional hazards survival regression analysis. The 5-year and 10-year OS rates were 38.4 and 33.1% for PSAC and 64.6 and 50.8% for PSCC, respectively. The 2-year and 5-year CSS rates were 60.6 and 45.9% for PSAC and 79.6 and 69.0% for PSCC, respectively. Patients with PSCC survive longer than PSAC patients and have other well-described prognostic factors for improved survival rates, including an early cancer stage, a younger patient age and standardised surgery.Impact statement Papillary serous adenocarcinoma of the uterine cervix (PSAC) and papillary squamous cell carcinoma (PSCC)are both very rare subtypes of cervical carcinomas. This retrospective population-based analysis has evaluated the survival outcomes and prognostic indicators of patients with PSAC and PSCC. Knowing the survival outcomes and prognostic indicators of PSAC and PSCC patients, we can better follow up patients.
Topics: Carcinoma, Papillary; Carcinoma, Squamous Cell; Cystadenocarcinoma, Serous; Female; Humans; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Rate; Uterine Cervical Neoplasms
PubMed: 34565276
DOI: 10.1080/01443615.2021.1945559 -
Neurological Research Mar 2024Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C (A3C) has been identified as a cancer molecular biomarker in the past decade. However, the...
BACKGROUND
Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C (A3C) has been identified as a cancer molecular biomarker in the past decade. However, the practical role of A3C in lower-grade gliomas (LGGs) in improving the clinical outcome remains unclear. This study aims to discuss the function of A3C in immunotherapy in LGGs.
METHODS
The RNA-Sequencing (RNA-seq) and corresponding clinical data were extracted from UCSC Xena and the results were verified in the Chinese Glioma Genome Atlas (CGGA). Weighted gene co-expression network analysis (WGCNA) was used for screening A3C-related genes. Comprehensive bioinformation analyses were performed and multiple levels of expression, survival rate, and biological functions were assessed to explore the functions of A3C.
RESULTS
A3C expression was significantly higher in LGGs than in normal tissues but lower than in glioblastoma (GBM), indicating its role as an independent prognosis predictor for LGGs. Twenty-eight A3C-related genes were found with WGCNA for unsupervised clustering analysis and three modification patterns with different outcomes and immune cell infiltration were identified. A3C and the A3C score were also correlated with immune cell infiltration and the expression of immune checkpoints. In addition, the A3C score was correlated with increased sensitivity to chemotherapy. Single-cell RNA (scRNA) analysis indicated that A3C most probably expresses on immune cells, such as T cells, B cells and macrophage.
CONCLUSIONS
A3C is an immune-related prognostic biomarker in LGGs. Developing drugs to block A3C could enhance the efficiency of immunotherapy and improve disease survival. A3C: Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C; LGGs: lower-grade gliomas; CGGA: Chinese Glioma Genome Atlas; WGCNA: Weighted gene co-expression network analysis; scRNA: Single-cell RNA; HGG: higher-grade glioma; OS: overall survival; TME: tumor microenvironment; KM: Kaplan-Meier; PFI: progression-free interval; IDH: isocitrate dehydrogenase; ROC: receiver operating characteristic; GS: gene significance; MM: module membership; TIMER: Tumor IMmune Estimation Resource; GSVA: gene set variation analysis; ssGSEA: single-sample gene-set enrichment analysis; PCA: principal component analysis; AUC: area under ROC curve; HAVCR2: hepatitis A virus cellular receptor 2; PDCD1: programmed cell death 1; PDCD1LG2: PDCD1 ligand 2; PTPRC: protein tyrosine phosphatase receptor type C; ACC: Adrenocortical carcinoma; BLCA: Bladder Urothelial Carcinoma;BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOLCholangiocarcinoma; COADColon adenocarcinoma; DLBC: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; ESCA: Esophageal carcinoma; GBM: Glioblastoma multiforme; HNSC: Head and Neck squamous cell carcinoma; KICH: Kidney Chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute Myeloid Leukemia; LGG: Brain Lower Grade Glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; OV: Ovarian serous cystadenocarcinoma; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and Paraganglioma; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; SARC: Sarcoma; SKCM: Skin Cutaneous Melanoma; STAD: Stomach adenocarcinoma; TGCT: Testicular Germ Cell Tumors; THCA: Thyroid carcinoma; THYM: Thymoma; UCEC: Uterine Corpus Endometrial Carcinoma; UCS: Uterine Carcinosarcoma; UVM: Uveal Melanoma.
Topics: Male; Female; Humans; Melanoma; Adenocarcinoma; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Uterine Cervical Neoplasms; Pancreatic Neoplasms; Skin Neoplasms; Urinary Bladder Neoplasms; Glioma; Glioblastoma; Biomarkers; Peptides; RNA; RNA, Messenger; Apolipoproteins; Prognosis; Cytidine Deaminase
PubMed: 38007705
DOI: 10.1080/01616412.2023.2287340 -
Hematology/oncology Clinics of North... Aug 2015Incidentally discovered pancreatic cystic lesions are increasingly common, affecting up to 10% to 15% of patients undergoing cross-sectional imaging. Although some... (Review)
Review
Incidentally discovered pancreatic cystic lesions are increasingly common, affecting up to 10% to 15% of patients undergoing cross-sectional imaging. Although some pancreatic cystic neoplasms harbor invasive malignancy or the potential to progress over time, a majority are benign and can be observed safely. Accurate diagnosis is key to appropriate management. Diagnosis requires a multidisciplinary and multimodal approach. This review discusses each type of pancreatic cystic neoplasm and the current data on diagnosis and treatment.
Topics: Cystadenocarcinoma; Cystadenoma; Humans; Pancreatic Cyst; Pancreatic Neoplasms; Prevalence; Risk Factors; Treatment Outcome
PubMed: 26226903
DOI: 10.1016/j.hoc.2015.04.002 -
Tumori Dec 2016Uterine papillary serous carcinoma (UPSC) is an atypical variant of endometrial carcinoma with a poor prognosis. It is commonly associated with an increased risk of... (Review)
Review
PURPOSE
Uterine papillary serous carcinoma (UPSC) is an atypical variant of endometrial carcinoma with a poor prognosis. It is commonly associated with an increased risk of extrauterine disease. The aim of this study was to investigate clinical and pathological characteristics, therapeutic methods, and prognostic factors in women with UPSC.
METHODS
All patients who underwent surgery for UPSC at a single high-volume cancer center between January 1995 and December 2010 were retrospectively reviewed. Patients who did not undergo surgical staging and those with mixed tumor histology were excluded. Univariate and multivariate regression models were used to identify the risk factors for overall survival (OS) and progression-free survival (PFS).
RESULTS
A total of 46 patients were included, the majority of whom having stage I disease (IA, 13 [28.2%] and IB, 12 [26.7%]). Stages II, III, and IV were identified in 5 (10.9%), 8 (17.4%), and 8 (17.4%) women, respectively. Optimal cytoreduction was obtained in 67.3% of patients. Recurrences developed in 8 (17.4%) patients. Multivariate analysis confirmed that lymphovascular space invasion (LVSI) (odds ratio [OR] 26.83, p = 0.003) was the only independent prognostic factor for OS, whereas LVSI and optimal cytoreduction were found to be independent prognostic factors for PFS (OR 6.91, p = 0.013 and OR 2.69, p = 0.037, respectively). The 5-year overall survival rate was 63%.
CONCLUSIONS
Our study demonstrated that LVSI is the only independent prognostic factor for OS, whereas LVSI and optimal cytoreduction are independent prognostic factors for PFS in patients with UPSC.
Topics: Aged; Biomarkers, Tumor; Combined Modality Therapy; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Female; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Recurrence; Retrospective Studies; Treatment Outcome; Uterine Neoplasms
PubMed: 27514313
DOI: 10.5301/tj.5000531 -
The American Journal of Surgical... Sep 2022The literature on liver cysts is highly conflicting, mostly owing to definitional variations. Two hundred and fifty-eight ≥1 cm cysts evaluated pathologically using...
The literature on liver cysts is highly conflicting, mostly owing to definitional variations. Two hundred and fifty-eight ≥1 cm cysts evaluated pathologically using updated criteria were classifiable as: I. Ductal plate malformation related (63%); that is, cystic bile duct hamartoma or not otherwise specified-type benign biliary cyst (35 with polycystic liver disease). These were female predominant (F/M=2.4), large (10 cm), often multifocal with degenerative/inflammatory changes and frequently misclassified as "hepatobiliary cystadenoma." II. Neoplastic (13%); 27 (10.5%) had ovarian-type stroma (OTS) and qualified as mucinous cystic neoplasm (MCN) per World Health Organization (WHO). These were female, solitary, mean age 52, mean size 11 cm, and 2 were associated with carcinoma (1 in situ and 1 microinvasive). There were 3 intraductal papillary neoplasms, 1 intraductal oncocytic papillary neoplasm, 1 cystic cholangiocarcinoma, and 2 cystic metastasis. III. Infectious/inflammatory (12%). These included 23 hydatid cysts (including 2 Echinococcus alveolaris both misdiagnosed preoperatively as cancer), nonspecific inflammatory cysts (abscesses, inflammatory cysts: 3.4%). IV. Congenital (7%). Mostly small (<3 cm); choledochal cyst (5%), foregut cyst (2%). V. Miscellaneous (4%). In conclusion, hepatic cysts occur predominantly in women (3/1), are mostly (90%) non-neoplastic, and seldom (<2%) malignant. Cystic bile duct hamartomas and their relative not otherwise specified-type benign biliary cysts are frequently multifocal and often misdiagnosed as "cystadenoma/carcinoma." Defined by OTS, MCNs (the true "hepatobiliary cystadenoma/carcinoma") are solitary, constitute only 10.5% of hepatic cysts, and have a significantly different profile than the impression in the literature in that essentially all are perimenopausal females, and rarely associated with carcinoma (7%). Since MCNs can only be diagnosed by demonstration of OTS through complete microscopic examination, it is advisable to avoid the term "cystadenoma/cystadenocarcinoma" solely based on radiologic examination, and the following simplified terminology would be preferable in preoperative evaluation to avoid conflicts with the final pathologic diagnosis: (1) noncomplex (favor benign), (2) complex (in 3 subsets, as favor benign, cannot rule out malignancy, or favor malignancy), (3) malignant features.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Choledochal Cyst; Cystadenocarcinoma; Cystadenoma; Cysts; Diagnosis, Differential; Female; Humans; Liver Diseases; Male; Middle Aged; Pancreatic Neoplasms
PubMed: 35778790
DOI: 10.1097/PAS.0000000000001930 -
Der Pathologe Feb 2015Cystic lesions of the pancreas are increasingly diagnosed with a reported prevalence of 10 % in 70-year-old individuals. Despite their broad spectrum, most resected... (Review)
Review
Cystic lesions of the pancreas are increasingly diagnosed with a reported prevalence of 10 % in 70-year-old individuals. Despite their broad spectrum, most resected cystic lesions can be attributed to one of the following entities: intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), neuroendocrine cystic tumors (NECT), and solid pseudopapillary neoplasms (SPN). Among them, IPMN and MCN represent precursors of ductal adenocarcinoma, NECT and SPN are low-grade, potentially malignant lesions, and SCN are usually benign. Due to the not negligible morbidity and mortality rates in pancreatic surgery, even in highly specialized centers, an interdisciplinary preoperative stratification of pancreatic cystic lesions into high- and low-risk tumors is necessary in order to accurately select those cases that need to undergo immediate resection. The role of the pathologist is fundamental in both the preoperative assessment and in the postoperative classification, which determines prognosis, further treatment, and follow-up.
Topics: Adenocarcinoma, Mucinous; Adult; Aged; Carcinoma, Papillary; Cooperative Behavior; Cystadenocarcinoma, Serous; Diagnosis, Differential; Female; Humans; Interdisciplinary Communication; Male; Middle Aged; Molecular Diagnostic Techniques; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms; Prognosis; Tertiary Care Centers
PubMed: 25663186
DOI: 10.1007/s00292-014-1971-6