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OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA ( CEACAM5 ) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. CONCLUSIONS: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.
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Cisto Pancreático , Neoplasias Pancreáticas , Humanos , RNA , Detecção Precoce de Câncer , Cisto Pancreático/diagnóstico , Cisto Pancreático/genética , Cisto Pancreático/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , DNA , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias PancreáticasRESUMO
BACKGROUND: Appendiceal mucinous neoplasms (AMNs) with disseminated disease (pseudomyxoma peritonei) are heterogeneous tumors with variable clinicopathologic behavior. Despite the development of prognostic systems, objective biomarkers are needed to stratify patients. With the advent of next-generation sequencing (NGS), it remains unclear if molecular testing can improve the evaluation of disseminated AMN patients. METHODS: Targeted NGS was performed for 183 patients and correlated with clinicopathologic features to include American Joint Committee on Cancer/World Health Organization (AJCC/WHO) histologic grade, peritoneal cancer index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS). RESULTS: Genomic alterations were identified for 179 (98%) disseminated AMNs. Excluding mitogen-activated protein kinase genes and GNAS due to their ubiquitous nature, collective genomic alterations in TP53, SMAD4, CDKN2A, and the mTOR genes were associated with older mean age, higher AJCC/WHO histologic grade, lymphovascular invasion, perineural invasion, regional lymph node metastasis, and lower mean PCI (p < 0.040). Patients harboring TP53, SMAD4, ATM, CDKN2A, and/or mTOR gene alterations were found to have lower OS rates of 55% at 5 years and 14% at 10 years, compared with 88% at 5 years and 88% at 10 years for patients without the aforementioned alterations (p < 0.001). Based on univariate and multivariate analyses, genomic alterations in TP53, SMAD4, ATM, CDKN2A, and/or the mTOR genes in disseminated AMNs were a negative prognostic factor for OS and independent of AJCC/WHO histologic grade, PCI, CC score, and hyperthermic intraperitoneal chemotherapy treatment (p = 0.006). CONCLUSIONS: Targeted NGS improves the prognostic assessment of patients with disseminated AMNs and identifies patients who may require increased surveillance and/or aggressive management.
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Adenocarcinoma Mucinoso , Neoplasias do Apêndice , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Humanos , Pseudomixoma Peritoneal/genética , Pseudomixoma Peritoneal/terapia , Pseudomixoma Peritoneal/metabolismo , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/terapia , Neoplasias do Apêndice/genética , Neoplasias do Apêndice/terapia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Serina-Treonina Quinases TOR/genética , Procedimentos Cirúrgicos de CitorreduçãoRESUMO
Colorectal carcinoma is a leading cause of cancer-related death worldwide. There is significant prognostic heterogeneity in stages II and III tumours, necessitating the development of new biomarkers to more clearly identify patients at risk of disease progression. Recently, the tumour immune environment, particularly the type and quantity of T lymphocytes, has been shown to be a useful biomarker in predicting prognosis for patients with colorectal carcinoma. In this review, the significance of the immune response in colorectal carcinoma, including its influence on prognosis and response to therapy, will be detailed.
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Neoplasias Colorretais , Linfócitos do Interstício Tumoral , Humanos , Prognóstico , Linfócitos do Interstício Tumoral/patologia , Neoplasias Colorretais/patologia , Contagem de Linfócitos , Imunidade , Linfócitos T CD8-PositivosRESUMO
BACKGROUND: Peritoneal dissemination of low-grade appendiceal mucinous neoplasms (LAMNs), sometimes referred to as pseudomyxoma peritonei, can result in significant morbidity and mortality. Little is known about the natural history of localized (non-disseminated) LAMNs. OBJECTIVE: The goal of this study was to evaluate the risk of peritoneal recurrence in patients with localized LAMNs. METHODS: We performed a multi-institutional retrospective review of patients with pathologically confirmed localized LAMNs. Baseline characteristics, pathology, and follow-up data were collected. The primary endpoint was the rate of peritoneal recurrence. RESULTS: We identified 217 patients with localized LAMNs. Median age was 59 years (11-95) and 131 (60%) patients were female. Surgical management included appendectomy for 124 (57.1%) patients, appendectomy with partial cecectomy for 26 (12.0%) patients, and colectomy for 67 (30.9%) patients. Pathology revealed perforation in 46 patients (37.7% of 122 patients with perforation status mentioned in the report), extra-appendiceal acellular mucin (EAM) in 49 (22.6%) patients, and extra-appendiceal neoplastic cells (EAC) in 13 (6.0%) patients. Median follow-up was 51.1 months (0-271). Seven (3.2%) patients developed a peritoneal recurrence, with a median time to recurrence of 14.4 months (2.5-47.0). Seven (15.2%) patients with histologic evidence of perforation had recurrence, versus no patients (0%) without perforation (p < 0.001); five (10.2%) patients with EAM versus two (1.2%) patients without EAM (p = 0.007), and one (7.7%) patient with EAC versus six (2.9%) patients without EAC (p = 0.355) had recurrence. CONCLUSIONS: This multi-institutional study represents the largest reported series of patients with localized LAMNs. In the absence of perforation or extra-appendiceal mucin or cells, recurrence was extremely rare; however, patients with any of these pathologic findings require careful follow-up.
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Adenocarcinoma Mucinoso , Neoplasias do Apêndice , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Adenocarcinoma Mucinoso/cirurgia , Neoplasias do Apêndice/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/cirurgia , Estudos RetrospectivosRESUMO
Gastrointestinal follicular lymphoma (GI-FL) is an uncommon non-Hodgkin lymphoma that affects the gastrointestinal tract. It typically occurs within the duodenum with the appearance of multiple nodules. Treatment options, depending on stage and grade of the tumor, include aggressive chemotherapy, immunotherapy, radiotherapy, surgical or endoscopic resection, or simply monitoring as focal disease may be indolent. We present a rare case of a GI-FL presenting as a solitary lesion within the cecum treated via endoscopic full-thickness resection using the Ovesco full-thickness resection device. This case demonstrates the effectiveness of endoscopic full-thickness resection in treating small GI-FL in the colon.
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The SWItch/Sucrose Non-Fermentable (SWI/SNF) complex is a multimeric protein involved in transcription regulation and DNA damage repair. SWI/SNF complex abnormalities are observed in approximately 14-34 % of pancreatic ductal adenocarcinomas (PDACs). Herein, we evaluated the immunohistochemical expression of a subset of the SWI/SNF complex proteins (ARID1A, SMARCA4/BRG1, SMARCA2/BRM, and SMARCB1/INI1) within our PDAC tissue microarray to determine whether SWI/SNF loss is associated with any clinicopathologic features or patient survival in PDAC. In our cohort, 13 of 353 (3.7 %) PDACs showed deficient SWI/SNF complex expression, which included 11 (3.1 %) with ARID1A loss, 1 (0.3 %) with SMARCA4/BRG1 loss, and 1 (0.3 %) with SMARCA2/BRM loss. All cases were SMARCB1/INI1 proficient. The SWI/SNF-deficient PDACs were more frequently identified in older patients with a mean age of 71.6 years (SD = 7.78) compared to the SWI/SNF-proficient PDACs which occurred at a mean age of 65.2 years (SD = 10.95) (P = 0.013). The SWI/SNF-deficient PDACs were associated with higher histologic grade, compared to the SWI/SNF-proficient PDACs (P = 0.029). No other significant clinicopathologic differences were noted between SWI/SNF-deficient and SWI/SNF-proficient PDACs. On follow-up, no significant differences were seen for overall survival and progression-free survival between SWI/SNF-deficient and SWI/SNF-proficient PDACs (both with P > 0.05). In summary, SWI/SNF-deficient PDACs most frequently demonstrate ARID1A loss. SWI/SNF-deficient PDACs are associated with older age and higher histologic grade. No other significant associations among other clinicopathologic parameters were seen in SWI/SNF-deficient PDACs including survival.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Idoso , Montagem e Desmontagem da Cromatina , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/genética , DNA Helicases , Proteínas Nucleares , Fatores de TranscriçãoRESUMO
Goblet cell adenocarcinoma is a rare appendiceal tumour with amphicrine differentiation that has distinct morphologic and clinical features compared to carcinomas seen elsewhere in the gastrointestinal tract. These tumors have engendered considerable confusion in the literature regarding their classification, and they have been described under several different names including goblet cell carcinoid, adenocarcinoid, and adenocarcinoma, among others. In the recent fifth edition of the World Health Organization Classification of Digestive System Tumors, goblet cell adenocarcinoma is the preferred diagnosis because of the increasing recognition of a frequent co-existing high-grade adenocarcinoma component. This review will present the clinicopathologic, molecular, and immunohistochemical features of goblet cell adenocarcinoma and discuss the current challenges in diagnosis, grading, and clinical management.
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Adenocarcinoma , Neoplasias do Apêndice , Apêndice , Tumor Carcinoide , Humanos , Apêndice/patologia , Células Caliciformes/patologia , Adenocarcinoma/patologia , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/patologia , Neoplasias do Apêndice/diagnóstico , Neoplasias do Apêndice/terapiaRESUMO
Multiplexed imaging technologies have made it possible to interrogate complex tumor microenvironments at sub-cellular resolution within their native spatial context. However, proper quantification of this complexity requires the ability to easily and accurately segment cells into their sub-cellular compartments. Within the supervised learning paradigm, deep learning based segmentation methods demonstrating human level performance have emerged. Here we present an unsupervised segmentation (UNSEG) method that achieves deep learning level performance without requiring any training data. UNSEG leverages a Bayesian-like framework and the specificity of nucleus and cell membrane markers to construct an a posteriori probability estimate of each pixel belonging to the nucleus, cell membrane, or background. It uses this estimate to segment each cell into its nuclear and cell-membrane compartments. We show that UNSEG is more internally consistent and better at generalizing to the complexity of tissue samples than current deep learning methods. This allows UNSEG to unambiguously identify the cytoplasmic compartment of a cell, which we employ to demonstrate its use in an example biological scenario. Within the UNSEG framework, we also introduce a new perturbed watershed algorithm capable of stably and accurately segmenting a cell nuclei cluster into individual cell nuclei. Perturbed watershed can also be used as a standalone algorithm that researchers can incorporate within their supervised or unsupervised learning approaches to replace classical watershed. Finally, as part of developing UNSEG, we have generated a high-quality annotated gastrointestinal tissue dataset, which we anticipate will be useful for the broader research community. Segmentation, despite its long antecedents, remains a challenging problem, particularly in the context of tissue samples. UNSEG, an easy-to-use algorithm, provides an unsupervised approach to overcome this bottleneck, and as we discuss, can help improve deep learning based segmentation methods by providing a bridge between unsupervised and supervised learning paradigms.
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The development of cross-sectional imaging techniques has enhanced the detection of pancreatic cystic lesions (PCLs). PCLs are found in approximately 2% of the general population, often as incidentally detected lesions on computed tomography or MRI during the evaluation of other medical conditions. Broadly, PCLs are classified as mucinous or nonmucinous. Mucinous PCLs include mucinous cystic neoplasms and intraductal papillary mucinous neoplasms. Nonmucinous PCLs include pseudocysts, serous cystadenomas, solid pseudopapillary neoplasms, and cystic pancreatic neuroendocrine tumors, as well as cystic acinar cell carcinoma, cystic degeneration of pancreatic ductal adenocarcinoma, lymphoepithelial cyst, and others.
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Carcinoma Ductal Pancreático , Cistadenoma Seroso , Cisto Pancreático , Neoplasias Pancreáticas , Pseudocisto Pancreático , Carcinoma Ductal Pancreático/patologia , Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/genética , Cistadenoma Seroso/patologia , Humanos , Cisto Pancreático/diagnóstico , Cisto Pancreático/genética , Cisto Pancreático/patologia , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Pseudocisto Pancreático/patologiaRESUMO
The serrated pathway of carcinogenesis has been the subject of intense investigation over the past 2 decades, but many gaps in our understanding still need to be resolved. Serrated polyp precursors include hyperplastic polyps, sessile serrated polyps, and traditional serrated adenomas. These are considered discrete entities, but there is emerging molecular data to suggest that they may be more closely related to each other than currently believed. The recent US Multi-Society Task Force surveillance guidelines for patients with serrated polyps are admittedly based on low quality evidence. In this brief review, we discuss the limitations in endoscopic detection and pathologic interpretation of serrated polyps and the implications of these diagnostic difficulties on risk prediction and postpolypectomy surveillance recommendations.
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Adenocarcinoma/patologia , Pólipos Adenomatosos/patologia , Transformação Celular Neoplásica/patologia , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Adenocarcinoma/cirurgia , Pólipos Adenomatosos/cirurgia , Animais , Biópsia , Colectomia , Pólipos do Colo/cirurgia , Colonoscopia , Neoplasias Colorretais/cirurgia , Progressão da Doença , Humanos , Hiperplasia , Valor Preditivo dos TestesRESUMO
CONTEXT.: Perineural invasion (PNI) by prostate cancer has been associated with adverse pathology, including extraprostatic extension. However, the significance of PNI quantification on prostate biopsy (PBx) remains unclear. OBJECTIVE.: To compare radical prostatectomy (RP) findings and long-term outcomes in patients whose PBx had exhibited PNI. DESIGN.: We assessed 497 consecutive patients undergoing sextant (6-site/≥12-core) PBx showing conventional adenocarcinoma followed by RP. RESULTS.: PNI was found in 1 (n = 290)/2 (n = 132)/3 (n = 47)/4 (n = 19)/5 (n = 5)/6 (n = 4) of the sites/regions of PBx. Compared with a single PNI site, multiple PNIs were significantly associated with higher preoperative prostate-specific antigen, higher Grade Group (GG) on PBx or RP, higher pT or pN category, positive surgical margin, and larger estimated tumor volume. When compared in subgroups of patients based on PBx GG, significant differences in RP GG (GG1-3), pT (GG1-2/GG1-3/GG2/GG3), surgical margin status (GG1-3/GG3/GG5), or tumor volume (GG1-2/GG1-3/GG2/GG3) between 1 versus multiple PNIs were observed. Moreover, there were significant differences in prostate-specific antigen (PNI sites: 1-2 versus 3-6/1-3 versus 4-6/1-4 versus 5-6), RP GG (1-3 versus 4-6/1-4 versus 5-6), pT (1-2 versus 3-6/1-3 versus 4-6), pN (1-3 versus 4-6), or tumor volume (1-2 versus 3-6/1-4 versus 5-6). Outcome analysis revealed significantly higher risks of disease progression in the entire cohort or PBx GG1-2/GG1-3/GG2/GG3/GG5 cases showing 2 to 6 PNIs, compared with respective controls with 1-site PNI. In multivariate analysis, multisite PNI was an independent predictor for progression (hazard ratio = 1.556, P = .03). CONCLUSIONS.: Multiple sites of PNI on PBx were associated with worse histopathologic features in RP specimens and poorer prognosis. PNI may thus need to be specified, if present, in every sextant site on PBx, especially those showing GG1-3 cancer.
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Antígeno Prostático Específico , Neoplasias da Próstata , Biópsia , Biópsia com Agulha de Grande Calibre , Humanos , Masculino , Gradação de Tumores , Prostatectomia/métodos , Neoplasias da Próstata/patologiaRESUMO
CONTEXT.: Grading small foci of prostate cancer on a needle biopsy is often difficult, yet the clinical significance of accurate grading remains uncertain. OBJECTIVE.: To assess if grading of limited adenocarcinoma on prostate biopsy specimen is critical. DESIGN.: We studied 295 consecutive patients undergoing extended-sextant biopsy with only 1-core involvement of adenocarcinoma, followed by radical prostatectomy. RESULTS.: The linear tumor lengths on these biopsy specimens were: less than 1 mm (n = 114); 1 mm or more or less than 2 mm (n = 82); 2 mm or more or less than 3 mm (n = 35); and 3 mm or more (n = 64). Longer length was strongly associated with higher Grade Group (GG) on biopsy or prostatectomy specimen, higher risk of extraprostatic extension/seminal vesicle invasion and positive surgical margin, and larger estimated tumor volume. When cases were compared based on biopsy specimen GG, higher grade was strongly associated with higher prostatectomy specimen GG, higher incidence of pT3/pT3b disease, and larger tumor volume. Outcome analysis further showed significantly higher risks for biochemical recurrence after radical prostatectomy in patients with 1 mm or more, 2 mm or more, 3 mm or more, GG2-4, GG3-4, GG4, less than 1 mm/GG2-4, less than 1 mm/GG3-4, less than 2 mm/GG3-4, 3 mm or more/GG2-4, or 3 mm or more/GG3-4 tumor on biopsy specimens, compared with respective control subgroups. In particular, 3 mm or more, GG3, and GG4 on biopsy specimens showed significance as independent prognosticators by multivariate analysis. Meanwhile, there were no significant differences in the rate of upgrading or downgrading after radical prostatectomy among those subgrouped by biopsy specimen tumor length (eg, <1 mm [44.7%] versus ≥1/<2 mm [41.5%] versus ≥2/<3 mm [45.7%] versus ≥3 mm [46.9%]). CONCLUSIONS.: These results indicate that pathologists still need to make maximum efforts to grade relatively small prostate cancer on biopsy specimens.
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Adenocarcinoma , Neoplasias da Próstata , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Biópsia , Biópsia com Agulha de Grande Calibre , Humanos , Masculino , Gradação de Tumores , Próstata/patologia , Próstata/cirurgia , Prostatectomia/métodos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgiaRESUMO
Although tumor-infiltrating T cells hold a beneficial prognostic role in colorectal cancer, other lymphocytic populations are less characterized. We developed a multiplexed immunofluorescence assay coupled with digital image analysis and machine learning to identify natural killer (NK) cells (NCAM1+CD3-), natural killer T-like (NKT-like) cells (NCAM1+CD3+), and T cells (NCAM1-CD3+) within the PTPRC+ (CD45+) cell population and to measure their granzyme B (GZMB; cytotoxicity marker) and FCGR3A (CD16a; NK-cell maturity marker) expression. We evaluated immune cell densities and spatial configuration in 907 incident colorectal carcinoma cases within two prospective cohort studies. We found that T cells were approximately 100 times more abundant than NK and NKT-like cells. Overall, NK cells showed high GZMB expression and were located closer to tumor cells than T and NKT-like cells. In T and NKT-like cells, GZMB expression was enriched in cells in closer proximity to tumor cells. Higher densities of both T and NKT-like cells associated with longer cancer-specific survival, independent of potential confounders (P trend < 0.0007). Higher stromal GZMB+ and FCGR3A+ NK-cell densities associated with longer cancer-specific survival (P trend < 0.003). For T and NKT-like cells, greater proximity to tumor cells associated with longer cancer-specific survival (P trend < 0.0001). These findings indicate that cytotoxic NCAM1+CD3-GZMB+ NK cells and NCAM1+CD3+ NKT-like cells are relatively rare lymphocytic populations within the colorectal cancer microenvironment and show distinct spatial configuration and associations with patient outcome. The results highlight the utility of a quantitative multimarker assay for in situ, single-cell immune biomarker evaluation and underscore the importance of spatial context for tumor microenvironment characterization.
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Neoplasias Colorretais , Células T Matadoras Naturais , Humanos , Células Matadoras Naturais , Prognóstico , Estudos Prospectivos , Microambiente TumoralRESUMO
Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in µm), crypt depth (CrD, in µm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.
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Doença Celíaca , Glutens , Biópsia , Dieta Livre de Glúten , Duodeno/patologia , Glutens/efeitos adversos , Humanos , Mucosa IntestinalRESUMO
BACKGROUND: Small cell neuroendocrine carcinoma of the prostate (SCNECP) is a rare, aggressive subtype of prostate carcinoma. Most SCNECP arise from conventional prostate adenocarcinoma (CPAC) treated with androgen deprivation therapy (ADT). CASE PRESENTATIONS: We identified four cases of CPAC treated with ADT, which evolved to SCNECP with liver metastasis. The average interval between the diagnosis of CPAC and SCNECP was 102 months (range: 12 to 168). Histologically, the tumors showed nests of cells with high nuclear:cytoplasmic ratios, granular chromatin, and frequent mitoses. All cases were synaptophysin, chromogranin, and AE1/AE3 positive, with a Ki-67 labeling index ≥70%. NKX3.1 was negative in all but one case and TTF-1 was positive in half. Weak ERG positivity by IHC was seen in one case which also demonstrated the TMPRSS2-ERG gene rearrangement; all other cases were negative for ERG by IHC. Serum prostate specific antigen (PSA) levels were normal to near-normal in all. The median interval between the diagnosis of SCNECP and death was 3.25 months (range: 0.75 to 26). CONCLUSIONS: Our case series highlights the importance of considering a prostate primary, even in the setting of normal PSA levels and loss of prostate markers, when diagnosing neuroendocrine carcinoma in the liver. Further, we emphasize the significance of diagnosing SCNECP that metastasizes to the liver, as it portends a particularly dismal prognosis.
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Carcinoma Neuroendócrino/secundário , Carcinoma de Células Pequenas/secundário , Transformação Celular Neoplásica/patologia , Neoplasias Hepáticas/secundário , Neoplasias da Próstata/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Antagonistas de Androgênios/uso terapêutico , Humanos , MasculinoRESUMO
Histiocytic sarcoma is a rare, but aggressive malignant neoplasm of monocyte/macrophage lineage with a wide age distribution. Bone involvement is exceedingly rarer compared to the lymph node, skin, and soft tissue, and no long bone involvement has been reported in the English literature. We here report 2 cases of histiocytic sarcoma involving the long bone: one from the femur of a 77-year-old female, status post the placement of an intramedullary nail for subtrochanteric hip fracture; the other from the radius of a 3-year-old female with no significant medical history. Radiologic imaging showed highly destructive lesions in both cases with soft-tissue extension. Microscopy in both cases showed sheets of polygonal mononuclear cells with abundant eosinophilic cytoplasm, prominent nucleoli, and frequent mitosis. Hemophagocytosis were also identified. Immunohistochemistry showed that the lesional cells were strongly diffusely positive for CD68 and CD163. The first patient deteriorated rapidly, despite the aggressive treatment of amputation and chemotherapy. However, the second patient is disease free 36 months post the treatment of amputation only. We conclude that the long bone could be the primary site of histiocytic sarcoma. Its prognosis could be very variable and it is difficult to predict its behavior based on morphological evaluation only.
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Neoplasias Ósseas/diagnóstico , Fêmur/patologia , Sarcoma Histiocítico/diagnóstico , Rádio (Anatomia)/patologia , Idoso , Amputação Cirúrgica , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Quimiorradioterapia Adjuvante , Pré-Escolar , Evolução Fatal , Feminino , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Sarcoma Histiocítico/patologia , Sarcoma Histiocítico/terapia , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/cirurgiaRESUMO
We present a case of a 69-year-old Hispanic male with a past medical history of type II diabetes mellitus who presented with a two-month history of abdominal pain. A CT scan was performed which identified a liver mass. Biopsy of the liver mass revealed infiltration of normal liver parenchyma by atypical glands surrounded by pale eosinophilic material. The atypical glands were positive for CK7, while negative for CK20, CDX-2, and TTF-1, consistent with intrahepatic cholangiocarcinoma. A Congo red stain was performed, which highlighted salmon-orange areas, some with a globular appearance, around the glands and within the sinusoids and vasculature. Under polarized light, these areas displayed apple-green birefringence. These findings were consistent with amyloidosis, which was further supported by identification of ALECT2- (leukocyte chemotactic factor-2-) type amyloid on mass spectrometry. To our knowledge, this is the first documented case of intrahepatic cholangiocarcinoma arising in association with LECT2 amyloidosis.
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Low-grade appendiceal mucinous neoplasm (LAMN) is an enigmatic tumor that lacks the capacity for classic invasion but can dissect through the appendiceal wall, causing pseudomyxoma peritonei (PMP). Most large studies of the histologic spectrum of LAMN and its rate of associated PMP include cases submitted from outside institutions, potentially skewing their findings. We identified 117 cases of LAMN at our institution. Hematoxylin and eosin-stained slides from each were reviewed, and clinical and pathologic parameters were noted. The patients were 76 females and 41 males, with a mean age of 60 years. Presenting symptoms were available for 113 patients; the majority (56%) were symptomatic, typically with abdominal pain. Ninety-one tumors (78%) were grossly dilated, and the entire appendix was submitted in 88 (75%) cases. Median lesion size was 5.5 cm. Ninety-two cases (79%) demonstrated epithelial denudation; these were often markedly dilated and contained intraluminal or mural microcalcifications. Thirty-two (27%) had a mucosal Schwann cell proliferation. On the basis of the American Joint Committee on Staging eighth edition cancer staging manual, of 117 cases, 66% were staged as pTis, 9% as pT3, 24% as pT4a, and 2% as pT4b. Ten cases (9%) were associated with histopathologic evidence of disseminated PMP. Only 1 patient died of disease, while 3 were alive with disease at last follow-up. Previous LAMN studies have utilized both departmental and extradepartmental material; our single-institution review demonstrated lower rates of PMP than some prior studies. Some LAMNs may be markedly dilated with extensive denudation, making the diagnosis difficult to confirm microscopically and ultimately requiring submission of the entire appendix for histologic evaluation.
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Adenocarcinoma Mucinoso/patologia , Neoplasias do Apêndice/patologia , Adenocarcinoma Mucinoso/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Apêndice/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pseudomixoma Peritoneal/epidemiologia , Pseudomixoma Peritoneal/etiologia , Adulto JovemRESUMO
Hepatocellular adenoma (HCA) is a rare benign tumor of the liver with low risk of malignant transformation. It is associated with oral contraceptives/anabolic steroid use, metabolic disease, and rarely, vascular abnormalities. We report an interesting case of HCA arising in a background of diffuse hepatic nodular regenerative hyperplasia (NRH) in a 40-year-old female patient with systemic lupus erythematosus (SLE). She presented with sudden-onset refractory ascites, elevated liver enzymes, diffuse hepatic nodularity and mass lesions on imaging concerning for malignancy. Targeted biopsies of the mass lesion were performed with inconclusive diagnoses. The patient ultimately underwent resection of the mass, which was confirmed as HCA, inflammatory type, arising in a background of NRH. It is not uncommon for SLE patients to have liver manifestations such as NRH, but HCA arising in NRH has not been previously reported. Our case reveals an unusual relationship between HCA and hepatic vasculopathy in the clinical context of a systemic inflammatory condition, the mechanism by which is not fully understood.