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1.
Pediatr Dev Pathol ; 27(3): 266-269, 2024.
Article in English | MEDLINE | ID: mdl-38178317

ABSTRACT

Serous cystadenoma is a rare lesion in the para-testicular tissue, with even rarer reports of this entity occurring in the scrotum post-orchidopexy. We present such an occurrence, adding support for its existence as a distinct entity.


Subject(s)
Cystadenoma, Serous , Genital Neoplasms, Male , Orchiopexy , Scrotum , Humans , Male , Scrotum/pathology , Cystadenoma, Serous/pathology , Cystadenoma, Serous/diagnosis , Cystadenoma, Serous/surgery , Genital Neoplasms, Male/pathology , Genital Neoplasms, Male/diagnosis , Genital Neoplasms, Male/surgery , Mullerian Ducts/pathology , Mullerian Ducts/abnormalities
2.
Ann Diagn Pathol ; 71: 152304, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38614035

ABSTRACT

INTRODUCTION: Differentiating pancreatic serous cystadenoma (SCA) from well-differentiated neuroendocrine tumors (WDNETs) based on histomorphology is critical yet challenging, particularly in small biopsy samples. Our study aimed to examine the expression profile of INSM1 in cytologic and surgical resection specimens from pancreatic SCA to evaluate its potential as a discriminative marker against pancreatic WDNET. METHODS: We characterized INSM1 immunohistochemistry in 34 patients with pancreatic SCA, comprising 23 surgical resections and 11 cytology specimens. As a control, we used 28 cytology specimens from pancreatic WDNET. Clinical information was retrieved through a review of electronic medical records. RESULTS: All 11 pancreatic SCA cytology specimens and 15 of 23 pancreatic SCA surgical resections exhibited absent INSM1 immunostaining. Each of the remaining eight surgical resection specimens demonstrated 1 % immunoreactivity. In contrast, 27 out of 28 (96 %) pancreatic WDNET cytology specimens were positive for INSM1 immunostaining, with a median immunoreactivity of 90 % and a range of 30-90 %. Overall, INSM1 immunostains perform similarly to chromogranin and synaptophysin in pancreatic SCA. CONCLUSIONS: The results indicate that INSM1 immunohistochemistry staining may serve as a useful neuroendocrine marker to differentiate pancreatic SCA from pancreatic WDNET in clinical practice. To our knowledge, this represents the first large-scale study to evaluate INSM1 immunostaining in surgical and cytology specimens from pancreatic SCA.


Subject(s)
Biomarkers, Tumor , Cystadenoma, Serous , Immunohistochemistry , Neuroendocrine Tumors , Pancreatic Neoplasms , Repressor Proteins , Humans , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/analysis , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/metabolism , Neuroendocrine Tumors/surgery , Female , Repressor Proteins/metabolism , Middle Aged , Male , Diagnosis, Differential , Aged , Cystadenoma, Serous/diagnosis , Cystadenoma, Serous/pathology , Cystadenoma, Serous/metabolism , Immunohistochemistry/methods , Adult , Aged, 80 and over , Synaptophysin/metabolism , Cytology
3.
Ann Surg Oncol ; 30(9): 5804-5812, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37249723

ABSTRACT

BACKGROUND: Over the years, the detection rate of pancreatic cystic neoplasms (PCNs) has significantly increased; however, the differential diagnosis and identification of high-risk PCNs remain challenging. We sought to investigate whether chromosomal instability (CIN) features in cell-free DNA in the cystic fluid of PCNs could help to identify high-risk PCNs. METHODS: Pancreatic cystic fluid samples from 102 patients with PCNs were intraoperatively collected for detection of CIN using an ultrasensitive chromosomal aneuploidy detector. Clinical and imaging data were retrospectively collected, and statistical analysis was performed to assess the potential role of CIN in clinical practice. RESULTS: CIN was investigated in a total of 100 patients. Sixteen of 26 serous cystic cystadenomas (SCAs) harbored deletions of chr3p and/or chr6p, whereas low rates of CIN were detected in mucinous cystic neoplasms. Most malignant PCNs presented with more than one type of CIN; amplification of chr1q and chr8q found in nine and seven of 11 malignant PCNs (81.8% and 63.6%), respectively, could aid in distinguishing high-risk IPMNs from low-risk ones, with a higher sensitivity than imaging. A combination of the mural nodule imaging feature and amplification of chr1q and chr8q achieved a sensitivity of 70.0% and a specificity of 82.4% in identifying high-risk IPMNs. CONCLUSIONS: Our work revealed the distinct CIN signature of different types of PCNs. Deletions of chr3p and chr6p defined a subtype of SCAs. Gains of chr1q and chr8q were associated with insidious malignant PCNs and helped identify high-risk IPMNs.


Subject(s)
Cystadenoma, Serous , Pancreatic Cyst , Pancreatic Neoplasms , Humans , Retrospective Studies , Pancreas/pathology , Pancreatic Neoplasms/surgery , Pancreatic Cyst/genetics , Pancreatic Cyst/diagnosis , Cystadenoma, Serous/genetics , Cystadenoma, Serous/diagnosis , Cystadenoma, Serous/pathology , Genomics
4.
Cytopathology ; 34(2): 99-105, 2023 03.
Article in English | MEDLINE | ID: mdl-36609991

ABSTRACT

OBJECTIVE: The molecular characteristics of low-grade serous carcinoma (LGSC) in serous effusions have not been studied previously. The present study analysed the molecular profile of LGSC at this anatomical site. METHODS: Specimens consisted of a series of 17 serous effusions (15 peritoneal, 2 pleural) from 16 patients, of which 15 were LGSC and 2 serous borderline tumour (SBT) who later progressed to LGSC. For comparative purposes, 9 surgical specimens from 6 patients with LGSC were analysed. Fresh-frozen cell pellets and surgical specimens underwent targeted next-generation sequencing covering 50 unique genes. RESULTS: Mutations were found in tumours from 14 of the 22 patients, of whom 4 had 2 different mutations and 10 had a single mutation. Overall, the most common mutations were in KRAS (n = 3) and BRAF (n = 3), followed by NRAS (n = 2), CDK2NA (n = 2), TP53 (n = 2), ATM (n = 2). Mutations in MET, STK11, ERBB2 and FLT3 were found in one case each. Patient-matched specimens had the same molecular profile. Both effusions with TP53 mutation had concomitant ATM mutation, and both stained immunohistochemically with a wild-type pattern. The absence of mutations was associated with a trend for shorter overall survival in univariate analysis (p = 0.072). CONCLUSIONS: The molecular alterations in LGSCs in serous effusions are consistent with those found in solid tumours, with frequent alterations in the mitogen-activated protein kinase pathway. Mutations in LGSC may be a marker of better outcomes.


Subject(s)
Cystadenocarcinoma, Serous , Cystadenoma, Serous , Ovarian Neoplasms , Peritoneal Neoplasms , Female , Humans , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/genetics , Cystadenocarcinoma, Serous/diagnosis , Cystadenocarcinoma, Serous/genetics , Mutation/genetics , Cystadenoma, Serous/pathology , Neoplasm Grading
5.
Pancreatology ; 22(7): 994-1002, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36089484

ABSTRACT

BACKGROUND: Although emerging data evidences that EUS-guided needle-based confocal laser endomicroscopy (nCLE) accurately diagnoses pancreatic cystic lesions (PCLs), there are a lack of interobserver agreement (IOA) studies utilizing reference histopathological diagnosis and for specific PCL subtypes. Hence, we sought to assess the IOA, intra-observer reliability (IOR), and diagnostic performance of EUS-nCLE using a large cohort of patients with histopathological diagnosis amongst a broad panel of international observers. METHODS: EUS-nCLE videos (n = 76) of subjects with PCLs [intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystadenoma (SCA), pseudocyst, and cystic-neuroendocrine tumors/solid pseudopapillary neoplasm (cystic-NET/SPN)], simulating clinical prevalence rates were obtained from 3 prospective studies. An international panel of 13 endosonographers with nCLE experience, blinded to all PCL data, evaluated the video library twice with a two-week washout for PCL differentiation (mucinous vs. non-mucinous) and subtype diagnosis. RESULTS: The IOA (κ = 0.82, 95% CI 0.77-0.87) and IOR (κ = 0.82, 95% CI 0.78-0.85) were "almost perfect" to differentiate mucinous vs. non-mucinous PCLs. For PCL subtype, IOA was highest for SCA (almost perfect; κ = 0.85), followed by IPMN (substantial, κ = 0.72), and cystic-NET/SPN (substantial, κ = 0.73). The IOA was moderate for MCN (κ = 0.47), and pseudocyst (κ = 0.57). Compared to histopathology, observers differentiated mucinous vs. non-mucinous PCLs with high accuracy (94.8%, 95% CI 93.3-96.1). For detecting specific PCLs subtypes, EUS-nCLE was highly accurate in diagnosing non-mucinous cysts (SCA: 98%; cystic-NET/SPN: 96%; pseudocyst: 96%) and slightly less accurate for mucinous lesions (IPMN: 86%; MCN: 84%). CONCLUSION: Diagnosis of PCLs by EUS-nCLE guided virtual biopsy is very accurate and reliable for the most prevalent pancreatic cysts in clinical practice.


Subject(s)
Cystadenoma, Serous , Neuroendocrine Tumors , Pancreatic Cyst , Pancreatic Intraductal Neoplasms , Pancreatic Neoplasms , Humans , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Prospective Studies , Reproducibility of Results , Microscopy, Confocal , Pancreatic Cyst/diagnostic imaging , Pancreatic Cyst/pathology , Cystadenoma, Serous/diagnostic imaging , Cystadenoma, Serous/pathology , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology
6.
Histopathology ; 79(2): 252-259, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33657658

ABSTRACT

AIMS: Because serous cystadenoma (SCA) does not usually require excision, it is critical to distinguish it from differential diagnoses which do, especially neuroendocrine tumour (NET). The gold standard for diagnosing SCA is assessment of endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNAB) material. Inhibin immunohistochemistry aids this assessment, but such positivity is not absolutely sensitive or specific to SCA. The following is the largest known study of SCA EUS-FNAB specimens and the first to compare four potential SCA immunomarkers between themselves and inhibin, compared against NET. METHODS AND RESULTS: Immunohistochemistry for calponin, mucin 6 (MUC6), glucose transporter 1 (GLUT1) and vascular endothelial growth factor A (VEGFA) was performed on 30 EUS-FNAB and three resection specimens of SCA and 32 EUS-FNAB specimens of NET. GLUT1 and VEGFA were suboptimal as diagnostic immunomarkers of SCA, being expressed by 10 and 44% of NETs, respectively. Further, their expression by cellular constituents of blood which often contaminate EUS-FNAB specimens hampered identification of neoplastic cells, especially in hypocellular samples. While 19% of NETs showed nuclear MUC6 positivity, cytoplasmic expression of the protein showed 100% specificity and sensitivity as an SCA marker. However, assessing MUC6 in EUS-FNAB specimens must also consider the protein's focal expression in physiological pancreatic, gastric or duodenal tissues, which can contaminate these specimens. Calponin was less sensitive (71% versus 100%) but more specific (100% versus 91%) than inhibin, although easier to assess in EUS-FNAB specimens than MUC6. CONCLUSIONS: Of the four potential immunomarkers of SCA suggested by the existing literature, calponin and MUC6 are useful complementary studies to inhibin for application to EUS-FNAB specimens.


Subject(s)
Calcium-Binding Proteins/metabolism , Cystadenoma, Serous/diagnosis , Cystadenoma, Serous/immunology , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Inhibins/metabolism , Microfilament Proteins/metabolism , Mucin-6/metabolism , Adolescent , Adult , Aged , Biomarkers, Tumor , Calcium-Binding Proteins/immunology , Cohort Studies , Cystadenoma, Serous/pathology , Duodenum/pathology , Endoscopic Ultrasound-Guided Fine Needle Aspiration/instrumentation , Female , Glucose Transporter Type 1/metabolism , Humans , Immunohistochemistry , Inhibins/immunology , Male , Microfilament Proteins/immunology , Middle Aged , Neuroendocrine Tumors/pathology , Pancreas/pathology , Stomach/pathology , Synaptophysin/metabolism , Vascular Endothelial Growth Factor A/metabolism , Calponins
7.
Reprod Biomed Online ; 43(2): 205-214, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34247989

ABSTRACT

RESEARCH QUESTION: What are ovarian stimulation cycle outcomes and acceptance rates of an oocyte accumulation programme in young women with benign ovarian tumour (BOT)? DESIGN: Retrospective cohort study conducted at the Academic Assisted Reproductive Technology and Fertility Preservation Centre, Lille University Hospital, between January 2016 and December 2019. The number of metaphase II oocytes per cycle and per patient after accumulation were evaluated. Two groups were identified for the analysis: endometrioma ('endometrioma') and dermoid, mucinous or serous cyst ('other cysts'). RESULTS: A total of 113 fertility-preservation cycles were analysed in 70 women aged 27.9 ± 4.8 years. Almost all women had undergone previous ovarian surgery before fertility preservation (89%). Mean anti-Müllerian hormone levels before ovarian stimulation was 12.5 ± 8.7 pmol/l. A total of 6.4 ± 3.4 oocytes were retrieved, and 4.3 ± 3.4 metaphase II (MII) oocytes were vitrified per cycle. All agreed to the oocyte accumulation programme and all underwent at least one cycle. To date, 36 (51%) patients achieved two or three fertility- preservation cycles. After accumulation, 7.0 ± 5.23 MII oocytes were vitrified per patient. No difference was found in ovarian response and oocyte cohort between the 'endometrioma' and 'other cysts' groups. Questionnaires completed after oocyte retrieval revealed abdominal bloating and pelvic pain in most patients, with no difference according to the type of cyst. No serious adverse events occurred. CONCLUSIONS: Oocyte accumulation should be systematically offered to young women with BOT irrespective of histological type, as it seems to be well-tolerated. Long-term follow-up is needed to assess the efficiency of oocyte accumulation to optimize the chances of subsequent pregnancies.


Subject(s)
Fertility Preservation/methods , Gynecologic Surgical Procedures/rehabilitation , Ovarian Cysts , Ovarian Neoplasms , Ovulation Induction , Adult , Cohort Studies , Cryopreservation/methods , Cystadenoma, Mucinous/complications , Cystadenoma, Mucinous/epidemiology , Cystadenoma, Mucinous/pathology , Cystadenoma, Mucinous/therapy , Cystadenoma, Serous/complications , Cystadenoma, Serous/epidemiology , Cystadenoma, Serous/pathology , Cystadenoma, Serous/therapy , Endometriosis/complications , Endometriosis/epidemiology , Endometriosis/pathology , Endometriosis/therapy , Female , Fertility Preservation/statistics & numerical data , Gynecologic Surgical Procedures/statistics & numerical data , Humans , Oocyte Retrieval/methods , Oocyte Retrieval/statistics & numerical data , Ovarian Cysts/complications , Ovarian Cysts/epidemiology , Ovarian Cysts/pathology , Ovarian Cysts/therapy , Ovarian Neoplasms/complications , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Ovarian Reserve/physiology , Ovary/surgery , Ovulation Induction/methods , Ovulation Induction/statistics & numerical data , Pregnancy , Retrospective Studies , Teratoma/complications , Teratoma/epidemiology , Teratoma/pathology , Teratoma/therapy , Treatment Outcome , Young Adult
8.
J Obstet Gynaecol ; 41(2): 248-253, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32285726

ABSTRACT

Ovarian cancer is the fifth leading cause of cancer-related mortality in women. Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme and there is growing evidence to suggest that it plays an important role in cancer progression. This is the first study to examine the expression of NNMT in serous ovarian cystadenomas, serous borderline tumours, low grade serous carcinomas (LGSC) and high grade serous carcinomas (HGSC) and investigate the potential independent association of NNMT expression with survival. Tissue samples were analysed immunohistochemically for NNMT expression. The stromal NNMT score was significantly higher in HGSC compared to serous cystadenomas and serous borderline tumours (p < .001, p < .043, respectively). The mean stromal NNMT score of patients with HGSC was significantly higher than patients with LGSC (p = .043). Patients with low expression of NNMT had a significantly higher mean recurrence-free survival than patients with high expression (p = .036). NNMT may support tumour progression in ovarian cancer by promoting desmoplastic stromal tumour reaction. NNMT overexpression may be associated with poor prognosis and can be a therapeutic target in ovarian cancer.IMPACT STATEMENTWhat is already known on this subject? Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that is overexpressed in many malignancies. Its overexpression was shown to lead to histone hypomethylation, which in turn can decrease and increase the expression of tumour suppressor proteins and onco-proteins, respectively. NNMT was also shown to play a role in epithelial-to-mesenchymal transition, which is critical in tumour progression and the stromal tumour reaction. The stromal tumour reaction was recently targeted with promising therapeutic results in ovarian cancer.What do the results of this study add? The expression of NNMT in various ovarian neoplasms including serous cystadenomas, borderline tumours and serous carcinomas has not been studied and independently associated with poor survival, previously. This study suggests that NNMT is progressively overexpressed in the stroma of ovarian neoplasms from benign cysts to HGSCs. NNMT overexpression appears to be independently associated with poor survival in ovarian cancer.What are the implications of these findings for clinical practice and/or further research? The implications of these findings are that NNMT may play an important role in the stromal tumour reaction, and therefore its overexpression may contribute to poor survival. NNMT overexpression may be an important target of ovarian cancer therapy.


Subject(s)
Carcinoma, Ovarian Epithelial , Cystadenocarcinoma, Serous , Cystadenoma, Serous , Nicotinamide N-Methyltransferase/metabolism , Ovarian Neoplasms , Adult , Biomarkers, Tumor/metabolism , Carcinoma, Ovarian Epithelial/genetics , Carcinoma, Ovarian Epithelial/mortality , Carcinoma, Ovarian Epithelial/pathology , Cystadenocarcinoma, Serous/genetics , Cystadenocarcinoma, Serous/mortality , Cystadenocarcinoma, Serous/pathology , Cystadenoma, Serous/genetics , Cystadenoma, Serous/mortality , Cystadenoma, Serous/pathology , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Middle Aged , Neoplasm Grading , Neoplasm Staging , Ovarian Neoplasms/genetics , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Prognosis , Survival Analysis , Transcriptome
9.
Pancreatology ; 20(5): 902-909, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32418758

ABSTRACT

BACKGROUND/OBJECTIVES: Pancreatic cystic neoplasms (PCNs) are common, among which 13%-23% are serous cystic neoplasms (SCNs). However, diffuse and multifocal variants of SCNs are extremely rare. The differential diagnosis of SCNs from other PCNs is important as the former entities are benign and do not become invasive. OBJECTIVE: This study analyzes the clinical characteristics of multifocal/diffuse SCN through a systematic review of the literature and a case report. METHODS: A comprehensive literature search was executed in the Ovid MEDLINE, Embase, and Google Scholar databases. The search strategy was designed to capture the concept of multifocal/diffuse SCN cases with sufficient clinical information for detailed analysis. Using the final included articles, we analyzed tumor characteristics, diagnostic modalities used, initial management and indications, and patient outcomes. RESULTS: A review of 262 articles yielded 19 publications with 22 cases that had detailed clinical information. We presented an additional case from our institution database. The systematic review of 23 cases revealed that the diffuse variant is more common than the multifocal variant (15 vs 8 cases, respectively). Patients were managed with surgical intervention, conservative treatment, or conservative treatment followed by surgical intervention. Indications for surgery following conservative management mainly included new onset or worsening of symptoms. Only one case reported significant tumor growth after attempting an observational approach. No articles reported recurrence of SCN after pancreatectomy, and no articles reported mortality related to multifocal/diffuse SCNs. CONCLUSION: Despite their expansive-growing and space-occupying characteristics, multifocal/diffuse SCNs should be treated similarly to their more common unifocal counterpart.


Subject(s)
Adenoma/epidemiology , Cystadenocarcinoma, Serous/epidemiology , Cystadenoma, Serous/epidemiology , Pancreatic Neoplasms/epidemiology , Adenoma/pathology , Adenoma/therapy , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/therapy , Cystadenoma, Serous/pathology , Cystadenoma, Serous/therapy , Humans , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy
10.
Gynecol Oncol ; 157(3): 783-792, 2020 06.
Article in English | MEDLINE | ID: mdl-32253045

ABSTRACT

OBJECTIVE: Cancer patient-derived organoids (PDOs) grow as three dimensional (3D) structures in the presence of extracellular matrix and have been found to represent the original tumor's genetic complexity. In addition, PDOs can be grown and subjected to drug sensitivity testing in a shorter time course and with lesser expense than patient-derived xenograft models. Many patients with recurrent ovarian cancer develop malignant effusions that become refractory to chemotherapy. Since these same patients often present for palliative aspiration of ascites or pleural effusions, there is a potential opportunity to obtain tumor specimens in the form of multicellular spheroids (MCS) present in malignant effusion fluids. Our objective was to develop a short duration culture of MCS from ovarian cancer malignant effusions in conditions selected to support organoid growth and use them as a platform for empirical drug sensitivity testing. METHODS: In this study, malignant effusion specimens were collected from patients with high-grade serous ovarian carcinoma (HGSOC). MCS were recovered and subjected to culture conditions designed to support organoid growth. In a subset of specimens, RNA-sequencing was performed at two time points during the short-term culture to determine changes in transcriptome in response to culture conditions. Organoid induction was also characterized in these specimens using Ki67 staining and histologic analysis. Drug sensitivity testing was performed on all specimens. RESULTS: Our model describes organoids formed within days of primary culture, which can recapitulate the histological features of malignant ascites fluid and can be expanded for at least 6 days. RNA-seq analysis of four patient specimens showed that within 6 days of culture, there was significant up-regulation of genes related to cellular proliferation, epithelial-mesenchymal transition, and KRAS signaling pathways. Drug sensitivity testing identified several agents with therapeutic potential. CONCLUSIONS: Short duration organoid culture of MCS from HGSOC malignant effusions can be used as a platform for empiric drug sensitivity testing. These ex vivo models may be helpful in screening new or existing therapeutic agents prior to individualized treatment options.


Subject(s)
Cystadenoma, Serous/pathology , Organ Culture Techniques/methods , Organoids/physiopathology , Aged , Cystadenoma, Serous/drug therapy , Female , Humans , Middle Aged , Neoplasm Grading , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology
11.
BMC Surg ; 20(1): 331, 2020 Dec 14.
Article in English | MEDLINE | ID: mdl-33317505

ABSTRACT

BACKGROUND: Serous cysto-adenoma (SCA) is a rare benign neoplasm of the pancreas. SCA can mimic other pancreatic lesions, such as neuroendocrine tumours. 68Gallium-DOTA-peptide Positron Emission Tomography (PET) is able to image in vivo the over-expression of the somatostatin receptors, playing an important role for the identification of neuroendocrine neoplasms. CASE PRESENTATION: We reported a case of 63-year-old man, with a solid lesion of 7 cm of diameter of the body-tail of the pancreas. Two fine-needle-aspirations (FNA) were inconclusive. A 68Ga-DOTA-peptide PET-CT revealed a pathological uptake of the pancreatic lesion. The diagnosis of a pancreatic neuroendocrine neoplasm was established and a laparoscopic distal splenopancreatectomy and cholecystectomy was performed. Final histopathological report revealed the presence of a micro-cystic SCA. CONCLUSIONS: The current case firstly reports a pancreatic SCA showing increased radiopharmaceutical uptake at 68Ga-DOTA-peptide PET-CT images. This unexpected finding should be taken into account during the diagnostic algorithm of a pancreatic lesion, in order to minimize the risk of misdiagnosis and overtreatment of SCA.


Subject(s)
Acetates/administration & dosage , Cystadenoma, Serous/diagnostic imaging , Gallium Radioisotopes/administration & dosage , Organometallic Compounds/metabolism , Pancreas/metabolism , Pancreatic Neoplasms/diagnostic imaging , Peptides, Cyclic/administration & dosage , Positron Emission Tomography Computed Tomography/methods , Cystadenoma, Serous/pathology , Cystadenoma, Serous/surgery , Humans , Male , Middle Aged , Neuroendocrine Tumors/diagnostic imaging , Pancreas/diagnostic imaging , Pancreas/pathology , Pancreatectomy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery
12.
Proteomics ; 19(21-22): e1800482, 2019 11.
Article in English | MEDLINE | ID: mdl-31364262

ABSTRACT

Epithelial ovarian cancer is one of the most fatal gynecological malignancies in adult women. As studies on protein N-glycosylation have extensively reported aberrant patterns in the ovarian cancer tumor microenvironment, obtaining spatial information will uncover tumor-specific N-glycan alterations in ovarian cancer development and progression. matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is employed to investigate N-glycan distribution on formalin-fixed paraffin-embedded ovarian cancer tissue sections from early- and late-stage patients. Tumor-specific N-glycans are identified and structurally characterized by porous graphitized carbon-liquid chromatography-electrospray ionization-tandem mass spectrometry (PGC-LC-ESI-MS/MS), and then assigned to high-resolution images obtained from MALDI-MSI. Spatial distribution of 14 N-glycans is obtained by MALDI-MSI and 42 N-glycans (including structural and compositional isomers) identified and structurally characterized by LC-MS. The spatial distribution of oligomannose, complex neutral, bisecting, and sialylated N-glycan families are localized to the tumor regions of late-stage ovarian cancer patients relative to early-stage patients. Potential N-glycan diagnostic markers that emerge include the oligomannose structure, (Hex)6 + (Man)3 (GlcNAc)2 , and the complex neutral structure, (Hex)2 (HexNAc)2 (Deoxyhexose)1 + (Man)3 (GlcNAc)2 . The distribution of these markers is evaluated using a tissue microarray of early- and late-stage patients.


Subject(s)
Biomarkers, Tumor/genetics , Cystadenoma, Serous/genetics , Ovarian Neoplasms/genetics , Polysaccharides/genetics , Biomarkers, Tumor/chemistry , Chromatography, Liquid , Cystadenoma, Serous/pathology , Female , Genomics/methods , Glycosylation , Humans , Molecular Imaging , Neoplasm Staging , Ovarian Neoplasms/pathology , Polysaccharides/chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Tumor Microenvironment/genetics
13.
Am J Gastroenterol ; 114(9): 1539-1549, 2019 09.
Article in English | MEDLINE | ID: mdl-31306149

ABSTRACT

OBJECTIVES: Pancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy. In pancreatic tissue and cyst fluid (CF) from PCLs, we sought to identify and validate novel methylated DNA markers (MDMs) that discriminate HGD/PC from low-grade dysplasia (LGD) or no dysplasia (ND). METHODS: From an unbiased whole-methylome discovery approach using predefined selection criteria followed by multistep validation on case (HGD or PC) and control (ND or LGD) tissues, we identified discriminant MDMs. Top candidate MDMs were then assayed by quantitative methylation-specific polymerase chain reaction on archival CF from surgically resected PCLs. RESULTS: Of 25 discriminant MDMs identified in tissue, 13 were selected for validation in 134 CF samples (21 cases [8 HGD, 13 PC], 113 controls [45 ND, 68 LGD]). A tree-based algorithm using 2 CF-MDMs (TBX15, BMP3) achieved sensitivity and specificity above 90%. Discrimination was significantly better by this CF-MDM panel than by mutant KRAS or carcinoembryonic antigen, with areas under the receiver operating characteristic curve of 0.93 (95% confidence interval: 0.86-0.99), 0.71 (0.57-0.85), and 0.72 (0.60-0.84), respectively. Cutoffs for the MDM panel applied to an independent CF validation set (31 cases, 56 controls) yielded similarly high discrimination, areas under the receiver operating characteristic curve = 0.86 (95% confidence interval: 0.77-0.94, P = 0.2). DISCUSSION: Novel MDMs discovered and validated in tissue accurately identify PCLs harboring HGD/PC. A panel of 2 MDMs assayed in CF yielded results with potential to enhance current risk prediction algorithms. Prospective studies are indicated to optimize and further evaluate CF-MDMs for clinical use.


Subject(s)
Carcinoma, Pancreatic Ductal/genetics , Cystadenoma, Serous/genetics , DNA Methylation/genetics , Pancreatic Cyst/genetics , Pancreatic Intraductal Neoplasms/genetics , Pancreatic Neoplasms/genetics , Precancerous Conditions/genetics , Aged , Bone Morphogenetic Protein 3/genetics , Carcinoembryonic Antigen/metabolism , Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/pathology , Cyst Fluid/metabolism , Cystadenoma, Serous/diagnosis , Cystadenoma, Serous/pathology , Female , Humans , Male , Middle Aged , Neoplasm Grading , Pancreatic Cyst/diagnosis , Pancreatic Cyst/pathology , Pancreatic Intraductal Neoplasms/diagnosis , Pancreatic Intraductal Neoplasms/pathology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Polymerase Chain Reaction , Precancerous Conditions/diagnosis , Precancerous Conditions/pathology , Proto-Oncogene Proteins p21(ras)/genetics , Reproducibility of Results , Sensitivity and Specificity , T-Box Domain Proteins/genetics
14.
Histopathology ; 74(4): 638-650, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30565721

ABSTRACT

AIMS: Low-grade serous carcinomas (LGSCs) and their precursors serous borderline tumours (SBTs) characteristically harbour mutations in BRAF, KRAS or NRAS but rarely in TP53, whereas high-grade serous carcinomas (HGSCs) are characterised by frequent TP53 mutations but rare BRAF, KRAS or NRAS mutations. In a small subset of cases, LGSCs and/or SBTs develop into high-grade tumours, including HGSCs and poorly differentiated carcinomas (PDCs). Here, we sought to define the repertoire of somatic genetic alterations in low-grade serous tumours and synchronous or metachronous high-grade adnexal carcinomas. METHODS AND RESULTS: DNA extracted from five SBTs/LGSCs and synchronous or metachronous HGSCs/PDCs and matched normal tissue was subjected to massively parallel sequencing targeting all exons and selected non-coding regions of 341 cancer-related genes. The low-grade and high-grade tumours from a given case were related, and shared mutations and copy number alterations. Progression from low-grade to high-grade lesions was observed, and involved the acquisition of additional mutations and/or copy number alterations, or shifts from subclonal to clonal mutations. Only two (an HGSC and a PDC) of the five high-grade tumours investigated harboured TP53 mutations, whereas NRAS and KRAS hotspot mutations were seen in two HGSCs and one HGSC, respectively. CONCLUSIONS: Our results suggest that progression from SBT to HGSC may take place in a subset of cases, and that at least some of the rare HGSCs lacking TP53 mutations may be derived from a low-grade serous precursor.


Subject(s)
Biomarkers, Tumor/genetics , Cystadenocarcinoma, Serous/genetics , Cystadenoma, Serous/genetics , Genital Neoplasms, Female/genetics , Adult , Aged , Aged, 80 and over , Cystadenocarcinoma, Serous/pathology , Cystadenoma, Serous/pathology , Disease Progression , Female , Genital Neoplasms, Female/pathology , Humans , Middle Aged , Neoplasm Grading , Neoplasms, Multiple Primary/pathology , Neoplasms, Second Primary/pathology
15.
BMC Cancer ; 19(1): 1223, 2019 Dec 16.
Article in English | MEDLINE | ID: mdl-31842793

ABSTRACT

BACKGROUND: Texture analysis of medical images has been reported to be a reliable method for differential diagnosis of neoplasms. This study was to investigate the performance of textural features and the combined performance of textural features and morphological characteristics in the differential diagnosis of pancreatic serous and mucinous cystadenomas. METHODS: We retrospectively reviewed 59 patients with pancreatic serous cystadenoma and 32 patients with pancreatic mucinous cystadenoma at our hospital. A three-dimensional region of interest (ROI) around the margin of the lesion was drawn manually in the CT images of each patient, and textural parameters were retrieved from the ROI. Textural features were extracted using the LifeX software. The least absolute shrinkage and selection operator (LASSO) method was applied to select the textural features. The differential diagnostic capabilities of morphological features, textural features, and their combination were evaluated using receiver operating characteristic (ROC) analysis, and the area under the receiver operating characteristic curve (AUC) was used as the main indicator. The diagnostic accuracy based on the AUC value is defined as follows: 0.9-1.0, excellent; 0.8-0.9, good; 0.7-0.8, moderate; 0.6-0.7, fair; 0.5-0.6, poor. RESULTS: In the differential diagnosis of pancreatic serous and mucinous cystadenomas, the combination of morphological characteristics and textural features (AUC 0.893, 95% CI 0.816-0.970) is better than morphological characteristics (AUC 0.783, 95% CI 0.665-0.900) or textural features (AUC 0.777, 95% CI 0.673-0.880) alone. CONCLUSIONS: In conclusion, our preliminary results highlighted the potential of CT texture analysis in discriminating pancreatic serous cystadenoma from mucinous cystadenoma. Furthermore, the combination of morphological characteristics and textural features can significantly improve the diagnostic performance, which may provide a reliable method for selecting patients with surgical intervention indications in consideration of the different treatment principles of the two diseases.


Subject(s)
Cystadenoma, Mucinous/diagnosis , Cystadenoma, Serous/diagnosis , Multidetector Computed Tomography , Pancreatic Neoplasms/diagnosis , Adolescent , Adult , Aged , Child , Child, Preschool , China , Cystadenoma, Mucinous/diagnostic imaging , Cystadenoma, Mucinous/pathology , Cystadenoma, Serous/diagnostic imaging , Cystadenoma, Serous/pathology , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Retrospective Studies , Young Adult
16.
BMC Cancer ; 19(1): 1267, 2019 Dec 30.
Article in English | MEDLINE | ID: mdl-31888566

ABSTRACT

BACKGROUND: Invasive mammary carcinomas that spontaneously develop in female cats are associated with high mortality, and resemble the most aggressive human breast cancers, especially triple-negative breast cancer (TNBC). Transcriptome studies showed that TNBCs are a heterogeneous group that includes a potentially hormone-dependent subtype named luminal-AR. Some authors proposed an immunohistochemical definition of the luminal-AR subtype, which is not only positive for Androgen Receptor (AR), but also either positive for the transcription factor Forkhead box A1 (FOXA1), or negative for basal markers. The objectives of this study were to describe AR and FOXA1 expressions in feline mammary carcinomas (FMCs), their prognostic value, and if their coexpression could define a "luminal-AR" subtype of triple-negative mammary carcinomas in cats. METHODS: In a previously described retrospective cohort of 180 female cats with FMCs, with a 2-year follow-up post-mastectomy, we assessed AR, FOXA1, ER, PR, Ki-67, HER2, and CK14 expressions by automated immunohistochemistry. RESULTS: Of the 180 FMCs, 57 (32%) were luminal; i.e., ER and/or PR positive, and 123 (68%) were triple-negative (ER-, PR- and HER2-) FMCs. AR overexpression (found in 33 cases/180, 18%) and FOXA1 index ≥1% (64/180, 36%) were associated with a longer disease-free interval, overall survival, and cancer-specific survival in cats with FMC. Analysis of AR, FOXA1 and CK14 coexpression in triple-negative FMCs showed that AR+ triple-negative FMCs were heterogeneous: there existed an AR+ FOXA1+ CK14- subgroup (n = 7) associated with a better cancer-specific survival by multivariate survival analysis (HR = 0.26, 95% CI: 0.07-0.89, p = 0.03) compared to AR+ FOXA1-CK14+ triple-negative FMCs (n = 46) (HR = 1.00), independently of the pathologic tumor size and pathologic nodal stage. The non-basal-like subtype of triple-negative FMCs that coexpresses AR and FOXA1 (the AR+ FOXA1+ CK14- subgroup) could represent the equivalent of the luminal-AR subgroup of human triple-negative breast cancer. CONCLUSIONS: We identified an AR+ FOXA1+ CK14- subgroup of triple-negative FMCs that might correspond to the luminal-AR subgroup of human triple-negative breast cancers. Cats with FMC may be interesting spontaneous animal models to investigate new strategies targeting the androgen receptor, especially in the aggressive subtype of AR+ basal-like triple-negative mammary carcinomas with loss of FOXA1 expression (the AR+ FOXA1-CK14+ subgroup).


Subject(s)
Breast Neoplasms/metabolism , Carcinoma, Squamous Cell/metabolism , Cystadenoma, Serous/metabolism , Hepatocyte Nuclear Factor 3-alpha/metabolism , Mammary Neoplasms, Animal/metabolism , Triple Negative Breast Neoplasms/metabolism , Animals , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cats , Cystadenoma, Serous/genetics , Cystadenoma, Serous/pathology , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic , Hepatocyte Nuclear Factor 3-alpha/genetics , Humans , Mammary Neoplasms, Animal/genetics , Mammary Neoplasms, Animal/pathology , Mastectomy , Neoplasms, Experimental , Phenotype , Prognosis , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Survival Analysis , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology
17.
BMC Gastroenterol ; 19(1): 127, 2019 Jul 16.
Article in English | MEDLINE | ID: mdl-31311499

ABSTRACT

BACKGROUND: To provide criteria for the differential diagnosis of serous cystic neoplasms (SCNs) and mucinous cystic neoplasms (MCNs) by analyzing the imaging features of these two neoplasms by endoscopic ultrasound (EUS). METHODS: From April 2015 to December 2017, a total of 69 patients were enrolled in this study. All patients were confirmed to have MCNs (31 patients) or SCNs (38 patients) by surgical pathology. All patients underwent EUS examination. The observation and recorded items were size, location, shape, cystic wall thickness, number of septa, and solid components. RESULTS: Head/neck location, lobulated shape, thin wall and > 2 septa were the specific imaging features for the diagnosis of SCNs. When any two imaging features were combined, we achieved the highest area under the curve (Az) (0.824), as well as the appropriate sensitivity (84.2%), specificity (80.6%), positive predictive value (PPV) (84.2%), and negative predictive value (NPV) (80.6%). Body/tail location, round shape, thick wall and 0-2 septa were the specific imaging features for the diagnosis of MCNs. When any three imaging features were combined, we obtained the highest Az value (0.808), as well as the appropriate sensitivity (77.4%), specificity (84.2%), PPV (80.0%) and NPV (82.1%). CONCLUSIONS: Pancreatic cystadenomas that meet any two of the four imaging features of head/neck location, lobulated shape, thin wall and > 2 septa could be diagnosed as SCNs, and those that meet any three of the four imaging features of body/tail location, round shape, thick wall and 0-2 septa could be considered as MCNs. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry. The registration identification number is ChiCTR-OOC-15006118 . The date of registration is 2015-03-20.


Subject(s)
Cystadenoma, Mucinous , Cystadenoma, Serous , Endosonography/methods , Pancreas/diagnostic imaging , Pancreatic Neoplasms , Adult , China , Cystadenoma, Mucinous/diagnosis , Cystadenoma, Mucinous/pathology , Cystadenoma, Serous/diagnosis , Cystadenoma, Serous/pathology , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Pancreas/pathology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Predictive Value of Tests , Prognosis , Prospective Studies , Sensitivity and Specificity
18.
Dig Dis Sci ; 64(12): 3616-3622, 2019 12.
Article in English | MEDLINE | ID: mdl-31290040

ABSTRACT

BACKGROUND AND AIMS: To determine the value of contrast-enhanced endoscopic ultrasound (CE-EUS) for differentiation of pancreatic cystic neoplasms (PCNs). METHODS: From April 2015 to December 2017, 82 patients were enrolled in this study. All patients were confirmed to have PCNs by surgical pathology. Prior to surgery, all patients underwent fundamental B-mode EUS (FB-EUS) and CE-EUS, 65 of whom underwent computed tomography (CT) and 71 of whom underwent magnetic resonance imaging (MRI). The enhanced mode data of PCNs were recorded. The diagnostic accuracy of CE-EUS in classifying PCNs was compared with that of CT, MRI and FB-EUS. The ability of CE-EUS to identify PCNs was evaluated by comparing the enhanced mode of PCNs. RESULTS: There was a significant difference between benign and malignant lesions in enhanced mode (P = 0.017). The enhanced modes of benign lesions were mostly type II and type III, while those of malignant lesions were type 0, type I, and type IV. The sensitivity, specificity, and accuracy of type 0, type I, and type IV enhanced mode as the diagnostic criterion for malignant lesions were 80%, 65.3%, and 67.1%, respectively. CE-EUS demonstrated greater accuracy in identifying PCNs than did CT, MRI, and FB-EUS (CE-EUS vs. CT: 92.3% vs. 76.9%; CE-EUS vs. MRI: 93.0% vs. 78.9%; CE-EUS vs. FB-EUS: 92.7% vs. 84.2%). CONCLUSION: Compared with CT, MRI, and FB-EUS, CE-EUS is better at differentiating PCNs. CE-EUS is expected to be another important imaging technique for the diagnosis of PCNs.


Subject(s)
Contrast Media , Cystadenocarcinoma/diagnostic imaging , Cystadenoma, Mucinous/diagnostic imaging , Cystadenoma, Serous/diagnostic imaging , Endosonography , Neuroendocrine Tumors/diagnostic imaging , Pancreatic Intraductal Neoplasms/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Adult , Cystadenocarcinoma/pathology , Cystadenoma, Mucinous/pathology , Cystadenoma, Serous/pathology , Diagnosis, Differential , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuroendocrine Tumors/pathology , Pancreatic Intraductal Neoplasms/pathology , Pancreatic Neoplasms/pathology , Phospholipids , Prospective Studies , Sensitivity and Specificity , Sulfur Hexafluoride , Tomography, X-Ray Computed
19.
BMC Pregnancy Childbirth ; 19(1): 523, 2019 Dec 26.
Article in English | MEDLINE | ID: mdl-31878899

ABSTRACT

BACKGROUND: Giant ovarian cyst is very rare in gravid-puerperium period. It is a cause of a maternal-fetal morbidity. We report a case of a giant benign ovarian cyst in gravid-puerperium period which was diagnosed and managed in a hospital of a low-resource country. CASE PRESENTATION: Data were collected by historical review, clinical examination, laboratory investigations, imaging examination, and by histopathological study of the excised surgical specimen. It is the case of a 25-year-old woman who was third gravida and third para with unknown pathological history. After she had given birth through vagina, a giant ovarian cyst, unknown during pregnancy, was diagnosed. A left oophorectomy carrying the cyst was performed after laparotomy in Yalgado Ouedraogo University Hospital Center of Ouagadougou (Burkina Faso). The cyst was 42 cm long and weighed 19.7 kg. The histology of the operative specimen revealed serous cystadenoma of the ovary. The postoperative course was uneventful. CONCLUSION: This case reports that vaginal delivery is possible with a giant ovarian cyst associated with pregnancy. Surgical management of the cyst can be performed in the postpartum with satisfaction.


Subject(s)
Cystadenoma, Serous/surgery , Ovarian Neoplasms/surgery , Ovariectomy , Postpartum Period , Pregnancy Complications, Neoplastic/surgery , Adult , Cystadenoma, Serous/diagnostic imaging , Cystadenoma, Serous/pathology , Delivery, Obstetric , Female , Humans , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/pathology , Pregnancy , Pregnancy Complications, Neoplastic/diagnostic imaging , Pregnancy Complications, Neoplastic/pathology , Tomography, X-Ray Computed , Tumor Burden , Ultrasonography
20.
Acta Radiol ; 60(4): 433-440, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30056739

ABSTRACT

BACKGROUND: Determining the growth rate of pancreatic cystic lesions on follow-up imaging is important in managing patients with these lesions. However, the growth rates of serous pancreatic neoplasms (SPNs) have been reported to vary among studies. PURPOSE: To determine the in vivo growth rate of SPNs. MATERIAL AND METHODS: This retrospective, single-institutional study included patients diagnosed with SPNs during 2006-2015. The diagnosis of SPNs was based on the results of surgery, endoscopic ultrasonography (EUS)-guided fine needle aspiration (FNA) or core needle biopsy (CNB), or typical radiologic features of SPN. A linear mixed-effects model was utilized to determine whether the diagnostic intervention was associated with tumor growth rate in all patients. The in vivo growth rate of SPNs was estimated from patients without or before diagnostic intervention. SPN growth rates were compared before and after diagnostic intervention. RESULTS: SPN growth rates in the overall patient cohort (n = 304) differed significantly between patients who did and did not undergo diagnostic interventions. The in vivo SPN growth rate in 204 patients without or before diagnostic intervention was 1.9 mm/year (95% confidence interval [CI] = 1.6-2.2). In the 130 patients who underwent diagnostic intervention, the SPN growth rate was significantly greater before than after diagnostic intervention (1.8 vs. 0.2 mm/year). CONCLUSIONS: In the absence of diagnostic intervention, the in vivo growth rate of SPNs was 1.9 mm/year (95% CI = 1.6-2.2). EUS-guided FNA or CNB may affect the growth rate of SPNs.


Subject(s)
Cystadenoma, Serous/diagnostic imaging , Cystadenoma, Serous/pathology , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle , Biopsy, Large-Core Needle , Endosonography/methods , Female , Humans , Male , Middle Aged , Pancreas/diagnostic imaging , Pancreas/pathology , Retrospective Studies , Young Adult
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