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Hepatobiliary mucoepidermoid carcinoma is a rare malignant tumor comprising mucous, intermediate, and epidermoid cells. Herein, we presented a case of primary liver mucoepidermoid carcinoma preoperatively misdiagnosed as conventional intrahepatic cholangiocarcinoma. A 67-year-old male was admitted to our hospital. Preoperative laboratory tests showed increased aspartate transaminase, alanine transaminase, and carbohydrate antigen 19-9. Abdominal Computer Tomography revealed a 4.8 × 4.9 cm liver mass in segment VI. A preliminary diagnosis of intrahepatic cholangiocarcinoma was made, with undergoing partial hepatectomy. However, on histopathology, the tumor comprised a mixture of epidermoid, mucous, and intermediate cells with diffuse infiltrating at the tumor margin. On special stains, mucous and intermedia cells were positive for mucicarmine and Alcian blue, whereas epidermoid cells were positive for Keratin 5/6 and p63. Intermediate cells are also positive for p63. All tumor cells were positive for Keratin 7. The Ki-67 index was 35%. The final diagnosis was primary hepatic mucoepidermoid carcinoma. Although rare, hepatic mucoepidermoid carcinoma should be considered in the intrahepatic cholangiocarcinoma differential diagnosis. We reviewed previous studies and found that hepatobiliary mucoepidermoid carcinoma is more likely to originate from the biliary tract adjacent to the tumor.
Assuntos
Carcinoma Mucoepidermoide , Neoplasias Hepáticas , Humanos , Masculino , Carcinoma Mucoepidermoide/patologia , Carcinoma Mucoepidermoide/diagnóstico , Carcinoma Mucoepidermoide/cirurgia , Carcinoma Mucoepidermoide/diagnóstico por imagem , Idoso , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Colangiocarcinoma/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Diagnóstico Diferencial , Tomografia Computadorizada por Raios XRESUMO
Intrahepatic cholangiocarcinoma (iCCA) exhibits different blood imaging features and prognosis depending on histology. To clarity histopathological growth patterns (HGPs) and vascularization processes of iCCA, we collected 145 surgical specimens and histologically classified them into large bile duct (LBD) (20 cases), small bile duct (SBD) (54), cholangiolocarcinoma (CLC) (35), combined SBD-CLC (cSBD-CLC) (26), and ductal plate malformation (DPM) (10) (sub)types. According to the invasive pattern at the interface between tumor and adjacent background liver, HGPs were classified into desmoplastic, pushing, and replacing HGPs. Desmoplastic HGP predominated in LBD type (55.5%), while replacing HGP was common in CLC (82.9%) and cSBD-CLC (84.6%) subtypes. Desmoplastic HGP reflected angiogenesis, while replacing HGP showed vessel co-option in addition to angiogenesis. By evaluating microvessel density (MVD) using vascular markers, ELTD1 identified vessel co-option and angiogenesis, and ELTD1-positive MVD at invasive margin in replacing HGP was significantly higher than those in desmoplastic and pushing HGPs. REDD1, an angiogenesis-related marker, demonstrated preferably higher MVD in the tumor center than in other areas. iCCA (sub)types and HGPs were closely related to vessel co-option and immune-related factors (lymphatic vessels, lymphocytes, and neutrophils). In conclusion, HGPs and vascular mechanisms characterize iCCA (sub)types and vessel co-option linked to the immune microenvironment.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neovascularização Patológica , Colangiocarcinoma/patologia , Colangiocarcinoma/irrigação sanguínea , Humanos , Neoplasias dos Ductos Biliares/patologia , Masculino , Feminino , Neovascularização Patológica/patologia , Pessoa de Meia-Idade , Idoso , Adulto , Densidade MicrovascularRESUMO
Immune-related adverse events (irAE) has been clarified according the usage of immune checkpoint inhibitors(ICI). We primarily found indoleamine 2,3-dioxygenase 1(IDO-1) as a histologic biomarker for the cholangiopathy of primary biliary cholangitis(PBC). In this study, we evaluated the utility of IDO-1 in identifying ICI-induced immune-mediated hepatotoxicity(IMH). Immunostaining for IDO-1 using liver sections of PBC, ICI-induced IMH and controls, revealed that IDO-1 expression in bile ducts is mostly restricted in PBC and ICI-induced IMH. In ICI-induced IMH, IDO-1-positive bile ducts is found in 2/2 cases of cholangitis type and also positive/focal ducts in 11/15 cases of hepatitis type. Moreover, in 8/13 positive/focal cases, ursodeoxycholic acid as well as steroids were needed to improve liver dysfunction, but just one case (1/4) in IDO-1-negative cases. One IDO-1 positive case of hepatitis type did not receive additional UDCA, but biliary enzymes worsen. In vitro study using cultured human biliary epithelial cells revealed that IDO-1 induction was found with the stimulation of IFN-γ. In conclusion, the presence of IDO-1-positive cells is found in bile ducts in hepatitic type as well as sclerosing cholangitis of ICI-induced IMH. IDO-1 is surely a valuable pathologic marker for diagnosing ICI-induced IMH and also for predicting an additional need of UDCA in clinical practice.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Ácido Ursodesoxicólico , Humanos , Ácido Ursodesoxicólico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Indolamina-Pirrol 2,3,-Dioxigenase , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológicoRESUMO
AIMS: Mass-forming intrahepatic cholangiocarcinomas (MF-iCCAs), involving small bile ducts, bile ductules or canals of Hering, remain treated as a single entity. We aimed to examine the diversity in histology, phenotype and tumour vasculature of MF-iCCAs. METHODS AND RESULTS: Based on morphology and immunophenotype, we classified MF-iCCAs into small bile duct (SBD), cholangiolocarcinoma (CLC), ductal plate malformation (DPM) and hepatocellular carcinoma (HCC)-like subtypes. Genetic correlations among the histological subtypes were examined by multi-region tumour sequencing. Vasculatures and other clinicopathological features were compared among tumour groups with various proportions of the histological subtypes in 62 MF-iCCAs. Cases of pure SBD, CLC, DPM and HCC-like subtypes numbered 18 (29%), seven (11.3%), none (0%) and two (3%), respectively; the remaining 35 (56.4%) cases comprised several components. Genetic alterations, isocitrate dehydrogenase (IDH)1/2, KRAS, TP53, polybromo-1 (PBRM1) and BRCA1-associated protein 1 (BAP1), were shared among SBD, CLC, DPM and hepatoid components within a tumour. We uncovered distinct vascularisation mechanisms among SBD, CLC and DPM subtypes with a prominent vessel co-option in CLC tumours. iCCA with a DPM pattern had the highest vascular densities (mean microvascular density,140/mm2 ; arterial vessel density, 18.3/mm2 ). Increased CLC component was correlated with longer overall survival time (r = 0.44, P = 0.006). Pure SBD tumours had a lower 5-year overall survival rate compared with MF-iCCA with CLC pattern (30.5 versus 72.4%, P = 0.011). CONCLUSIONS: MF-iCCAs comprise four histological subtypes. Given their sharing some driver gene alterations, indicating they can have a common cell origin, SBD, CLC and DPM subtypes, however, differ in cell differentiation, histology, phenotype or tumour vasculature.
Assuntos
Colangiocarcinoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Diferenciação Celular , Colangiocarcinoma/classificação , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Feminino , Histocitoquímica , Humanos , Isocitrato Desidrogenase/genética , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Vasos Retinianos/patologia , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genéticaRESUMO
AIM: Presently, no standardized definition or acceptable diagnostic criteria have been established for acute presentation of autoimmune hepatitis (AP-AIH), making it difficult to differentiate that condition from drug-induced liver injury (DILI). This study aimed to characterize clinical and histological features for distinguishing between AP-AIH and DILI. METHODS: Clinical, biochemical, and histological characteristics of AP-AIH and DILI in clinically well-characterized cases were compared in a standardized manner to clarify differences. RESULTS: In clinical evaluations, immunoglobulin G level and rate of anti-nuclear antibody positivity were greater in AP-AIH than DILI cases. As for diagnosis of each condition, significant (P < 0.01) differences were found for 10 features: lobular necrosis/inflammation, cobblestone appearance of hepatocytes, plasma cell infiltration in liver parenchyma, centrilobular fibrosis, hepatic rosette formation in areas with cobblestone appearance, portal inflammation, interface hepatitis, prominent plasma cells in portal areas, bile duct injury, and hepatic rosette formation in periportal areas. The area under the curve and cut-off values for the combination of these 10 features were 0.95 and 9 (sensitivity 86%, specificity 90%), respectively. CONCLUSION: Combinations of histological features were found to be helpful for differentiating AP-AIH from DILI, but we were not able to statistically identify an individual feature as definitive.
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Biliary epithelial cells preferentially respond to various insults under chronic pathological conditions leading to reactively atypical changes, hyperplasia, or the development of biliary neoplasms (such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and cholangiocarcinoma). Moreover, benign biliary strictures can be caused by a variety of disorders (such as IgG4-related sclerosing cholangitis, eosinophilic cholangitis, and follicular cholangitis) and often mimic malignancies, despite their benign nature. In addition, primary sclerosing cholangitis is a well-characterized precursor lesion of cholangiocarcinoma and many other chronic inflammatory disorders increase the risk of malignancies. Because of these factors and the changes in biliary epithelial cells, biliary strictures frequently pose a diagnostic challenge. Although the ability to differentiate neoplastic from non-neoplastic biliary strictures has markedly progressed with the advance in radiological modalities, brush cytology and bile duct biopsy examination remains effective. However, no single modality is adequate to diagnose benign biliary strictures because of the low sensitivity. Therefore, understanding the underlying causes by compiling the entire clinical, laboratory, and imaging data; considering the under-recognized causes; and collaborating between experts in various fields including cytopathologists with multiple approaches is necessary to achieve an accurate diagnosis.
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Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/diagnóstico , Adulto , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Colangite/diagnóstico , Colangite/patologia , Constrição Patológica , Diagnóstico Diferencial , HumanosRESUMO
A well-documented Achilles heel of current cancer immunotherapy approaches is T cell exhaustion within solid tumor tissues. The proinflammatory cytokine interleukin (IL)-23 has been utilized to augment chimeric antigen receptor (CAR) T cell survival and tumor immunity. However, in-depth interrogation of molecular events downstream of IL-23/IL-23 receptor signaling is hampered by a paucity of suitable cell models. The current study investigates the differential contribution of IL-2 and IL-23 to the maintenance and differentiation of the IL-23 responsive Kit225 T-cell line. We observed that IL-23 enhanced cellular fitness and survival but was insufficient to drive proliferation. IL-23 rapidly induced phosphorylation of STAT1, STAT3, and STAT4, and messenger RNA expression of IL17A, the archetypal effector cytokine of T helper 17 (Th17) cells, but not their lineage markers RORC and NCR1. These observations suggest that IL-23 endowed Th17/ILC3-like effector function but did not promote their differentiation. In contrast, spontaneous differentiation of Kit225 cells toward a Th17/ILC3-like phenotype was induced by prolonged IL-2 withdrawal. This was marked by strongly elevated basal IL17A and IL17F expression and the secretion of IL-17. Together, our data present Kit225 cells as a valuable model for studying the interplay between cytokines and their contribution to T cell survival, proliferation, and differentiation.
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Diferenciação Celular , Interleucina-23 , Interleucina-2 , Células Th17 , Humanos , Linhagem Celular , Proliferação de Células , Sobrevivência Celular , Interleucina-17/metabolismo , Interleucina-17/imunologia , Interleucina-2/farmacologia , Interleucina-23/metabolismo , Interleucina-23/imunologia , Transdução de Sinais , Células Th17/imunologiaRESUMO
Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA.
Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Aprendizado Profundo , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Estudos RetrospectivosRESUMO
Introduction: Angiosarcoma of pancreas is an extremely rare disease with a poor prognosis. The clinical signs and symptoms of pancreatic angiosarcoma are nonspecific, and it is occasionally diagnosed at an advanced stage. Pancreatic angiosarcoma and Pancreatic ductal adenocarcinoma in one patient was never ever known in English literature. Case presentation: A 56-year-old female was admitted with clinical and laboratory signs of gastrointestinal (GI) bleeding. Upper gastrointestinal endoscopy revealed bleeding from the ampulla of Vater. Besides, abdominal computed tomographic (CT) revealed a solid mass in the region of the pancreatic tail, which was considered the origin of bleeding. Distal pancreatectomy and splenectomy were performed because of persistent GI bleeding, and the final histological diagnosis of tumor in pancreatic tail was pancreatic ductal adenocarcinoma. After 30 days, she developed recurrent bleeding in ampulla and the abdominal CT-scan revealed a huge hematoma in omentum harem. We conducted transcatheter arterial embolization, but anemia continued to worsen. Therefore, pancreaticoduodenectomy was recommended to remove this mass, and based on postoperative histological findings, pancreatic angiosarcoma was diagnosed. After few days, laparotomy was indicated again because of persistent intra-abdominal bleeding. Despite all critical care and surgical therapeutic attempts, the patient died within two weeks after operation. Discussion: A pancreatic angiosarcomas primary origin is especially rare, with the present case being the tenth accounted in the English literature. Angiosarcomas is creating a disorganized mass of cells with extravasated blood that led to characteristics, extensive amounts of hemorrhage. The clinical manifestations of pancreatic angiosarcoma are variable, and immunohistochemistry staining is mandatory, with positive staining for vascular markers, which include CD31, CD34, von Willebrand factor (vWF), factor-VIII, Ulex europaeus agglutinin 1 (UEA-1), Friend leukemia integration 1 (Fli-1) and vascular endothelial growth factor receptor (VEGFER). Conclusion: We here present a report of an extremely rare case with had pancreatic angiosarcoma and synchronous pancreatic ductal adenocarcinoma with clinical picture of GI bleeding secondary to hemosuccus pancreaticus (HP).
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Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that can involve multiple organs. It is often challenging to distinguish IgG4-related sclerosing cholangitis (IgG4-SC) from cholangiocarcinoma because of overlap in their clinical findings. A 75-year-old man presented to a hospital for a detailed examination of the elevation of some biliary enzymes. Radiographic examination revealed segmental bile duct with wall thickening of the common hepatic bile duct, and dilation of the peripheral branches. Transampullary biopsy showed a non-specific inflammatory reaction with several IgG4-positive cell infiltrations. There were no signs of malignancy. The liver biopsy showed bile duct injury accompanied by IgG4-positive cell infiltration. We then performed bile duct biopsy and finally diagnosed the patient with cholangiocarcinoma. We should remember that the IgG4 reaction is neither completely sensitive nor specific for IgG4-RD and avoid resting solely on the IgG4 reaction to precisely distinguish IgG4-SC from cholangiocarcinoma.
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Aim: Causes, clinical features, and diagnostic approaches for small bowel (SB) bleeding were analyzed to derive recommendations in dealing with this clinical condition. Methods: We included 54 patients undergoing surgical treatment for SB bleeding, from January 2009 to December 2019. Detailed clinical data, diagnosis procedures, and causes of bleeding were collected. Results: Among 54 cases with SB bleeding, the most common causes were tumors (64.8%), followed by angiopathy (14.8%), ulcers (9.3%), diverticula (5.6%), tuberculosis (3.7%), and enteritis (1.9%). Most tumors (32/35 cases, 91.4%) and vascular lesions (8/8 cases, 100%) were located in the jejunum. The incidence of tumors was higher in the older (30/41 cases, 73.1%) than that in patients younger than 40 years of age (5/13 cases, 38.5%, P < 0.01). Common initial findings were melena (68.5%) and hematochezia (31.5%). The overall diagnostic yield of computed tomographic enterography (CTE) was 57.4% (31/54 cases), with the figures for tumors, vascular lesions, and inflammatory lesions being 71.4% (25/35 cases), 62.5% (5/8 cases), and 12.5% (1/8 cases), respectively. Double-balloon enteroscopy (DBE) definitively identified SB bleeding sources in 16/22 (72.7%) patients. Conclusion: Tumors, angiopathy, ulcers, and diverticula were the most common causes of SB bleeding in Northern Vietnamese population. CTE has a high detection rate for tumors in patients with SB bleeding. CTE as a triage tool may identify patients before double-balloon enteroscopy because of the high prevalence of SB tumors.
Assuntos
Enteroscopia de Duplo Balão , Intestino Delgado , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/etiologia , Humanos , Intestino Delgado/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , VietnãRESUMO
AIMS: Although liver biopsy is crucial to diagnose and guide treatment decisions, a detailed histological analysis of autoimmune hepatitis (AIH) with clinically acute presentations has not yet been performed. This study aimed to characterise the histological features and explore potential histological hallmarks to diagnose the acute presentation of AIH. METHODS: We systematically evaluated liver specimens of 87 adult patients with acute presentation of AIH retrospectively enrolled from Japanese multicentre facilities. Each histological feature was predefined by consensus based on the diagnostic criteria. RESULTS: Key findings were that acute presentation of AIH revealed histological features of both acute hepatitis and chronic hepatitis accompanying various degrees of fibrosis. The prominent features were lobular necrosis/inflammation (97.7%), plasma cell infiltration (96.4%), emperipolesis (89.3%), pigmented macrophages (84.5%), cobblestone appearance of hepatocytes (82.6%) and perivenular necroinflammatory activity, including centrilobular necrosis (81.4%). CONCLUSIONS: The acute presentation of AIH represents the entire histological spectrum of acute hepatitis and chronic hepatitis with various activity grades and fibrosis stages that clinically correspond to acute-onset AIH and acute exacerbation of classic AIH, respectively. Although there are no pathognomonic features for the pathological diagnosis, the prominent presence of lobular and perivenular necroinflammatory activity, pigmented macrophages and cobblestone appearance of hepatocytes in addition to the classic AIH features, such as plasma cell infiltration and emperipolesis, are useful for the pathological diagnosis of the acute presentation of AIH.