RESUMO
AIMS: Advanced liver fibrosis can regress following the elimination of causative injuries. Trichrome (TC) stain has traditionally been used to evaluate the degree of fibrosis in liver, although it is rarely helpful in assessing quality of fibrosis (i.e. progression and regression). Orcein (OR) stain highlights established elastic fibres, but its use in examining fibrosis is not well recognised. This study assessed the potential utility of comparing OR and TC staining patterns to evaluate the quality of fibrosis in various settings of advanced fibrosis. METHODS AND RESULTS: The haematoxylin and eosin and TC stains of 65 liver resection/explant specimens with advanced fibrosis caused by different elements were reviewed. Twenty-two cases were scored as progressive (P), 16 as indeterminate (I) and 27 as regressive (R) using TC stain based on the Beijing criteria. The OR stains confirmed 18 of 22 P cases. The remaining P cases showed either stable fibrosis or mixed P and R. Of the 27 R cases, 26 were supported by OR stain, with many showing thin perforated septa typically seen in adequately treated viral hepatitis cases. The 16 I cases showed a variety of OR staining patterns, which allowed for further subclassification than using TC stain alone. Viral hepatitis cases were enriched for regressive features (17 of 27). CONCLUSIONS: Our data demonstrated the utility of OR as an adjunctive stain to evaluate the changes in fibrosis in cases of cirrhosis.
Assuntos
Corantes , Cirrose Hepática , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Fígado/patologia , Fibrose , Coloração e RotulagemRESUMO
The molecular classification of hepatocellular adenomas highlights a distinctive genotype-phenotype correlation. Malignant transformation is an exceptionally rare complication of hepatocyte nuclear factor 1α (HNF1A)-inactivated hepatocellular adenomas. This subtype is characterized by loss of liver fatty acid binding protein immunoexpression. In this study, we characterized the histopathologic spectrum of 13 liver fatty acid binding protein-deficient hepatocellular adenoma cases showing malignant transformation from multiple centers. Clinicopathologic characteristics of these patients were evaluated. Stains for reticulin, liver fatty acid binding protein, beta-catenin and glutamine synthetase were applied to these lesions. Moreover, the findings were compared to patients with ß-catenin mutated hepatocellular adenoma. Liver fatty acid binding protein-deficient hepatocellular adenomas with borderline features/carcinoma were seen predominantly in females (77%) with an average age of 46 ± 18 years and multiple lesions (77%; five patients with adenomatosis). Meanwhile, ß-catenin mutated hepatocellular adenoma patients with malignant transformation were predominantly male (67%, p = 0.018) with single lesion (86%, p = 0.0009). The largest liver fatty acid binding protein-deficient hepatocellular adenoma nodule in each patient ranged from 4 to 15.5 cm. Loss of liver fatty acid binding protein by immunohistochemistry was noted in all adenoma and borderline/carcinoma components. Features of malignant transformation were pseudoglandular architecture (85%), cytologic atypia (85%), architectural atypia (100%) and lack of steatosis (100%). Other findings included myxoid change (39%), peliosis (46%) and sinusoidal dilatation (46%). Molecular studies confirmed somatic inactivation of HNF1A in 3 cases and absence of TERT promotor and exon 3 CTNNB1 mutations in five cases. To summarize, liver fatty acid binding protein-deficient hepatocellular adenoma with malignant transformation is most frequently seen in female patients with multiple lesions. Most of these lesions demonstrate pseudoglandular architecture, cytologic and architectural atypia, with lack of steatosis. The natural history of these lesions is relatively benign with the exception of disease recurrence in 1 patient.
Assuntos
Adenoma de Células Hepáticas/química , Biomarcadores Tumorais/deficiência , Transformação Celular Neoplásica/química , Proteínas de Ligação a Ácido Graxo/deficiência , Neoplasias Hepáticas/química , Adenoma de Células Hepáticas/genética , Adenoma de Células Hepáticas/patologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Cromograninas/genética , Europa (Continente) , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Inativação Gênica , Fator 1-alfa Nuclear de Hepatócito/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos , Fatores Sexuais , Telomerase/genética , Estados Unidos , Adulto Jovem , beta Catenina/genéticaRESUMO
AIMS: The aim of this study was to perform a comprehensive retrospective analysis of liver transplant biopsies with parenchymal rejection (PR) at our institution, including histological features, laboratory values and follow-up biopsies, and to compare PR with portal-based acute cellular rejection (ACR). METHODS AND RESULTS: Biopsies from 173 patients were evaluated (retrospective database search 1990-2017), including 49 isolated PR, 35 PR with portal ACR (PR/ACR), 34 mild ACR and 52 moderate ACR cases. The rise and fall of serum liver enzymes was calculated as a measure of acute liver injury and response to immunotherapy, respectively. Isolated PR was associated with delayed-onset acute rejection (P < 0.001), as well as younger age (P = 0.004), and showed a similar rise in liver enzymes to mild ACR. PR/ACR and moderate ACR showed the highest elevations in transaminases (P < 0.05). Isolated PR on an initial biopsy was associated with recurrent episodes of PR (P = 0.01), chronic ductopaenic rejection (P = 0.002) and chronic vascular rejection (P = 0.017). Immunohistochemistry for C4d was performed, and strong C4d staining of venules was only detected in one severe isolated PR case (one of three, 33%) and one moderate ACR case (one of 20, 5%). CONCLUSIONS: Isolated PR represents a form of late acute rejection with distinct clinical and histological features. There is value in reporting PR in liver transplant biopsies to identify patients at higher risk of developing recurrent PR and chronic rejection. Standardisation of terminology and histological criteria of PR can help in uniform reporting and ensure appropriate management.
Assuntos
Rejeição de Enxerto/patologia , Transplante de Fígado , Fígado/patologia , Adolescente , Adulto , Idoso , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Combined hepatocellular-cholangiocarcinomas (CHC) are mixed tumours with both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) components. CHC prognosis is similar to intrahepatic CC (ICC) and worse than HCC; staging and treatment generally follow ICC algorithms. However, the molecular biology of CHC remains poorly characterised. We performed capture-based next-generation sequencing of 20 CHC and, for comparison, 10 ICC arising in cirrhosis. Intratumour heterogeneity was assessed by separately sequencing the HCC and CC components of nine CHC. CHC demonstrated molecular profiles similar to HCC, even in the CC component. CHC harboured recurrent alterations in TERT (80%), TP53 (80%), cell cycle genes (40%; CCND1, CCNE1, CDKN2A), receptor tyrosine kinase/Ras/PI3-kinase pathway genes (55%; MET, ERBB2, KRAS, PTEN), chromatin regulators (20%; ARID1A, ARID2) and Wnt pathway genes (20%; CTNNB1, AXIN, APC). No CHC had alterations in IDH1, IDH2, FGFR2 or BAP1, genes typically mutated in ICC. TERT promoter mutations were consistently identified in both HCC and CC components, supporting TERT alteration as an early event in CHC evolution. TP53 mutations were present in both components in slightly over half the TP53-altered cases. By contrast, focal amplifications of CCND1, MET and ERRB2, as well as Wnt pathway alterations, were most often exclusive to one component, suggesting that these are late events in CHC evolution. ICC in cirrhosis demonstrated alterations similar to ICC in non-cirrhotic liver, including in IDH1 or IDH2 (30%), CDKN2A (40%), FGFR2 (20%), PBRM1 (20%), ARID1A (10%) and BAP1 (10%). TERT promoter and TP53 mutation were present in only one ICC each. Our data demonstrate that CHC genetics are distinct from ICC (even in cirrhosis) and similar to HCC, which has diagnostic utility and implications for treatment. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Colangiocarcinoma/genética , Perfilação da Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Complexas Mistas/genética , Transcriptoma , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/patologia , Feminino , Dosagem de Genes , Rearranjo Gênico , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias Complexas Mistas/patologiaRESUMO
Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare vascular liver disease that has attracted new interest in recent years. It is characterised by clinical signs of portal hypertension in the absence of cirrhosis or severe fibrosis and any known cause of portal hypertension. As much uncertainty exists about INCPH pathophysiology, and no definite diagnostic tests are available, liver biopsy is an essential tool for achieving a definite diagnosis. Unfortunately, the histological diagnosis of INCPH is not always straightforward, as the characteristic lesions are unevenly distributed, vary greatly in their severity, are often very subtle, and are not all necessarily present in a single case. Furthermore, specifically for the characteristic portal vessel changes observed in INCPH, the terminology and definition are ambiguous, which adds complexity to the already complex clinicopathological scenario. An international study group of liver pathologists and hepatologists pursued a consensus on nomenclature for the portal vascular lesions of INCPH. Such standardisation may assist pathologists in the recognition of such lesions, and will possibly facilitate further advancement in this field.
Assuntos
Hipertensão Portal/patologia , Fígado/patologia , HumanosRESUMO
Simplified criteria for diagnosis of autoimmune hepatitis are based on autoantibodies, serum immunoglobulin G, histologic features, and negative viral serology. A score of 6 points is necessary for the designation of probable autoimmune hepatitis and 7 points or more for definite autoimmune hepatitis. The presence of three histologic features is required for categorizing a case as typical (2 points): interface hepatitis with portal lymphocytic/lymphoplasmacytic cells extending into lobule, emperipolesis, and rosettes. In the absence of all three features, a chronic hepatitis picture is considered compatible with autoimmune hepatitis (1 point). This study examines the validity of these histologic features for the diagnosis of autoimmune hepatitis. Clinical data and liver biopsies were reviewed for 88 autoimmune hepatitis, 20 primary biliary cholangitis, and 13 non-autoimmune acute hepatitis cases. Interface/lobular activity, number of plasma cells, copper/CK7 stains, and presence/absence of biliary features were assessed in autoimmune hepatitis and primary biliary cholangitis cases. The simplified criteria score was calculated. Modified histologic criteria were formulated on the basis of interface/lobular activity, number of plasma cells, and presence/absence of biliary features. Using the proposed histologic features, histologic score of 2 increased from 8 to 77%, while total simplified score of >6 increased from 69 to 86%. There was no increase in total simplified score for primary biliary cholangitis or non-autoimmune acute hepatitis. Rosettes and emperipolesis are difficult to interpret, and lack sensitivity and sensitivity for autoimmune hepatitis diagnosis. The current histologic criteria used in the current simplified score lead to underscoring of autoimmune hepatitis cases. The modified histologic criteria based on the inflammatory activity, extent of plasma cells, and results of copper/CK7 staining increased the histologic score in autoimmune hepatitis and led to a probable/definite diagnosis of autoimmune hepatitis in 17% of cases that would have otherwise been classified as non- autoimmune hepatitis by simplified score.
Assuntos
Hepatite Autoimune/diagnóstico , Hepatite Autoimune/patologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
While non-alcoholic steatohepatitis is a slowly progressive disease, patients may rarely present in acute liver failure. We describe six patients who developed severe hepatic dysfunction following rapid weight loss or malnutrition. Rapid weight loss (18 to 91 kg) occurred after Roux-en-Y gastric bypass in four patients and starvation-like dieting or hypoalbuminemia was noted in two patients. Four patients either died or received an urgent liver transplant. Pathologic findings were characterized by advanced alcoholic steatohepatitis-like features, including extensive/circumferential centrizonal pericellular fibrosis, central scar with perivenular sclerosis/veno-occlusion with superimposed hepatocellular dropout, abundant/prominent hepatocellular balloons, and numerous Mallory-Denk bodies, but there was no history of excess alcohol consumption. This study characterizes clinicopathologic features of aggressive non-alcoholic steatohepatitis following rapid weight loss or malnutrition, which should be included in the differential diagnosis with alcohol when a patient is considered for liver transplantation. The mechanism of liver injury in aggressive steatohepatitis is unknown, but rapid fat mobilization in obese patients may potentially cause oxidative stress to the liver and further study is needed to determine if there is a genetic predisposition to this form of injury and if antioxidants may protect the liver during rapid weight loss/malnutrition.
Assuntos
Dieta com Restrição de Carboidratos/efeitos adversos , Dieta Rica em Proteínas/efeitos adversos , Derivação Gástrica/efeitos adversos , Fígado/patologia , Desnutrição/etiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Redução de Peso , Adulto , Diagnóstico Diferencial , Progressão da Doença , Feminino , Derivação Gástrica/mortalidade , Humanos , Fígado/cirurgia , Transplante de Fígado , Desnutrição/diagnóstico , Desnutrição/mortalidade , Desnutrição/fisiopatologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/mortalidade , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Estado Nutricional , Valor Preditivo dos Testes , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Hepatocyte nuclear factor-1α mutated hepatocellular adenomas (H-HCA) are thought to have no to minimal malignant potential. This report describes a 23-year-old woman with maturity-onset diabetes of the young who developed a 12.5-cm hepatic mass with a radiographically and pathologically distinct 3.0-cm region. Histologically and immunohistochemically, the bulk of the mass was an H-HCA with extensive pseudoglandular formation and only focal steatosis. The 3.0-cm nodule showed small cell change, thickened hepatocyte plates, pleomorphic and hyperchromatic nuclei, reticulin loss, and stromal and vascular invasion, diagnostic of hepatocellular carcinoma (HCC). Immunohistochemically, increased expression of glutamine synthetase in tumor cells and CD34 expression in sinusoidal endothelial cells were seen in the HCC component. Nuclear expression of ß-catenin, and exon 3 of CTNNB1 and TERT promoter mutations were absent in this case. Thus, we report a HCC arising in an H-HCA; although cases appear exceedingly rare, they reinforce the potential of H-HCA for malignant transformation.
Assuntos
Adenoma de Células Hepáticas/diagnóstico , Carcinoma Hepatocelular/diagnóstico , Transformação Celular Neoplásica , Diabetes Mellitus Tipo 2/complicações , Fator 1-alfa Nuclear de Hepatócito/genética , Neoplasias Hepáticas/diagnóstico , Fígado/patologia , Neoplasias Primárias Múltiplas/diagnóstico , Adenoma de Células Hepáticas/complicações , Adenoma de Células Hepáticas/genética , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/genética , Feminino , Humanos , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/genética , Neoplasias Primárias Múltiplas/genética , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Immunotactoid deposits are defined by their ultrastructural appearance and are characterized by microtubular or cylindrical structures typically measuring greater than 30 nm in diameter. Although a rare entity, immunotactoid deposition most often manifests as immunotactoid glomerulopathy and is associated with underlying lymphoplasmacytic disorders. Corneal immunotactoid deposition known as immunotactoid keratopathy has also been reported in patients with paraproteinemia. Here, we describe the first reported case of immunotactoid deposition in the stomach. The deposits were composed solely of kappa immunoglobulin light chains without significant lambda light chain or immunoglobulin heavy chain components. The patient displayed no renal signs or symptoms, and additional thorough clinical examination failed to detect any evidence of a paraproteinemia or plasma cell dyscrasia. Thus, the gastric immunotactoid deposits in this case appear to be an isolated finding of light chain deposition, of which the significance and etiology are unclear.
Assuntos
Cadeias kappa de Imunoglobulina , Antro Pilórico/patologia , Gastropatias/imunologia , Gastropatias/patologia , Comorbidade , Feminino , Hepatite C/epidemiologia , Humanos , Imuno-Histoquímica , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Antro Pilórico/imunologiaRESUMO
Well-differentiated hepatocellular carcinoma in non-cirrhotic liver can show morphological features similar to hepatocellular adenoma. In rare instances, hepatocellular carcinoma can arise in the setting of hepatocellular adenoma. This study compares the immunohistochemical and cytogenetic features of the hepatocellular adenoma-like and hepatocellular carcinoma portions of these tumors. Immunohistochemistry for ß-catenin, glutamine synthetase, serum amyloid A protein, glypican-3, and heat-shock protein 70 was done in 11 cases of hepatocellular carcinoma arising in hepatocellular adenoma in non-cirrhotic liver. Tumors with nuclear ß-catenin and/or diffuse glutamine synthetase were considered ß-catenin activated. Fluorescence in situ hybridization (FISH) was done in nine cases for gains of chromosomes 1, 8 and MYC. There were seven men (33-75 years) and four women (29-65 years). Focal atypical morphological features were seen in hepatocellular adenoma-like areas in 7 (64%) cases. Hepatocellular adenoma-like areas showed features of inflammatory hepatocellular adenoma in 7 (64%) cases; 4 of these were also serum amyloid A-positive in the hepatocellular carcinoma portion. ß-Catenin activation, heat-shock protein 70 positivity, and chromosomal gains on FISH were seen in the hepatocellular adenoma portion in 55%, 40%, and 56% of cases, and 73%, 60%, and 78% of cases in the hepatocellular carcinoma portion, respectively. In conclusion, the hepatocellular adenoma-like portion of most cases of hepatocellular carcinoma arising in hepatocellular adenoma shows features typically seen in hepatocellular carcinoma such as focal morphological abnormalities, ß-catenin activation, heat-shock protein 70 expression, and chromosomal gains. Hepatocellular adenoma-like areas in these tumors, especially in men and older women, may represent an extremely well-differentiated variant of hepatocellular carcinoma, whereas the morphologically recognizable hepatocellular carcinoma portion represents a relatively higher grade component of the tumor.
Assuntos
Adenoma de Células Hepáticas/diagnóstico , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Hepáticas/diagnóstico , Neoplasias Complexas Mistas/diagnóstico , Adenoma de Células Hepáticas/química , Adenoma de Células Hepáticas/genética , Adenoma de Células Hepáticas/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Diferenciação Celular , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 8 , Feminino , Glutamato-Amônia Ligase/análise , Glipicanas/análise , Proteínas de Choque Térmico HSP70/análise , Humanos , Neoplasias Hepáticas/química , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Complexas Mistas/química , Neoplasias Complexas Mistas/genética , Neoplasias Complexas Mistas/patologia , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas c-myc/genética , Proteína Amiloide A Sérica/análise , beta Catenina/análiseRESUMO
Inflammatory hepatocellular adenoma can show overlapping histological features with focal nodular hyperplasia, including inflammation, fibrous stroma, and ductular reaction. Expression of serum amyloid-associated protein in inflammatory hepatocellular adenoma and map-like pattern of glutamine synthetase in focal nodular hyperplasia can be helpful in this distinction, but the pitfalls and limitations of these markers have not been established. Morphology and immunohistochemistry were analyzed in 54 inflammatory hepatocellular adenomas, 40 focal nodular hyperplasia, and 3 indeterminate lesions. Morphological analysis demonstrated that nodularity, fibrous stroma, dystrophic blood vessels, and ductular reaction were more common in focal nodular hyperplasia, while telangiectasia, hemorrhage, and steatosis were more common in inflammatory hepatocellular adenoma, but there was frequent overlap of morphological features. The majority of inflammatory hepatocellular adenomas demonstrated perivascular and/or patchy glutamine synthetase staining (73.6%), while the remaining cases had diffuse (7.5%), negative (3.8%), or patchy pattern of staining (15%) that showed subtle differences from the classic map-like staining pattern and was designated as pseudo map-like staining. Positive staining for serum amyloid-associated protein was seen in the majority of inflammatory hepatocellular adenomas (92.6%) and in the minority of focal nodular hyperplasia (17.5%). The glutamine synthetase staining pattern was map-like in 90% of focal nodular hyperplasia cases, with the remaining 10% of cases showing pseudo map-like staining. Three cases were labeled as indeterminate and showed focal nodular hyperplasia-like morphology but lacked map-like glutamine synthetase staining pattern; these cases demonstrated a patchy pseudo map-like glutamine synthetase pattern along with the expression of serum amyloid-associated protein. Our results highlight the diagnostic errors that can be caused by variant patterns of staining with glutamine synthetase and serum amyloid-associated protein in inflammatory hepatocellular adenoma and focal nodular hyperplasia.
Assuntos
Adenoma de Células Hepáticas/diagnóstico , Biomarcadores Tumorais/análise , Hiperplasia Nodular Focal do Fígado/diagnóstico , Glutamato-Amônia Ligase/análise , Imuno-Histoquímica , Neoplasias Hepáticas/diagnóstico , Proteína Amiloide A Sérica/análise , Adenoma de Células Hepáticas/química , Adenoma de Células Hepáticas/enzimologia , Adenoma de Células Hepáticas/patologia , Adolescente , Adulto , Idoso , Biópsia , Proteína C-Reativa/análise , Criança , Pré-Escolar , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Hiperplasia Nodular Focal do Fígado/enzimologia , Hiperplasia Nodular Focal do Fígado/patologia , Humanos , Mediadores da Inflamação/análise , Neoplasias Hepáticas/química , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to describe the presenting symptoms, endoscopic and histologic findings, and clinical courses of pediatric patients diagnosed with solitary rectal ulcer syndrome (SRUS). METHODS: We describe 15 cases of SRUS diagnosed at our institution during a 13-year period. Cases were identified by review of a pathology database and chart review and confirmed by review of biopsies. Data were collected by retrospective chart review. RESULTS: Presenting symptoms were consistent but nonspecific, most commonly including blood in stools, diarrhea alternating with constipation, and abdominal/perianal pain. Fourteen of 15 patients had normal hemoglobin/hematocrit, erythrocyte sedimentation rate, and albumin at diagnosis. Endoscopic findings, all limited to the distal rectum, ranged from erythema to ulceration and polypoid lesions. Histology revealed characteristic findings. Stool softeners and mesalamine suppositories improved symptoms, but relapse was common. CONCLUSIONS: SRUS in children presents with nonspecific symptoms and endoscopic findings. Clinical suspicion is required, and diagnosis requires histologic confirmation. Response to present treatments is variable.
Assuntos
Doenças Retais/diagnóstico , Úlcera/diagnóstico , Adolescente , Anti-Inflamatórios não Esteroides/uso terapêutico , Criança , Feminino , Seguimentos , Humanos , Doenças Inflamatórias Intestinais/complicações , Laxantes/uso terapêutico , Masculino , Mesalamina/uso terapêutico , Proctoscopia , Doenças Retais/complicações , Doenças Retais/tratamento farmacológico , Recidiva , Estudos Retrospectivos , Supositórios/uso terapêutico , Síndrome , Resultado do Tratamento , Úlcera/complicaçõesRESUMO
The distinction between well-differentiated intrahepatic cholangiocarcinoma (iCCA) from its morphological mimics such as bile duct adenoma (BDA) and hamartoma (BDH) can be challenging, particularly in small biopsies. Although a few cases of BDA and BDH have been reported to undergo malignant transformation into iCCA, their neoplastic versus benign nature remains debated. DNA flow cytometry was performed on 47 formalin-fixed paraffin-embedded samples of iCCA, 14 BDA, and 18 BDH. Aneuploidy was detected in 22 iCCA (47%) but in none of the 32 BDA and BDH samples. Among the 34 iCCA patients who underwent complete resection and were followed up to tumor recurrence, tumor-related death, or at least for 1 year, the overall recurrence or death rates (regardless of flow cytometric results) were 18, 56, and 71% within 1, 3, and 5 years, respectively. The 1-, 3-, and 5-year recurrence or death rates in 18 iCCA patients with aneuploidy were 28, 66, and 66%, respectively, whereas 16 iCCA patients in the setting of normal DNA content had 1-, 3-, and 5-year rates of 6, 44, and 72%, respectively. Although aneuploid tumors were associated with worse outcomes during the first 3 years, this difference was not statistically significant (hazard ratio = 1.4, p = 0.473) in the present sample size. In conclusion, the frequency of aneuploidy was significantly higher in iCCA (47%) than in its benign morphological mimics (0%), suggesting that it may potentially serve as a diagnostic marker of malignancy in challenging situations. Our findings also suggest that most BDAs and BDHs, if not all, are benign entities and may not represent precursor lesions to iCCAs that often harbor aneuploidy. Although a larger cohort will be necessary to further determine the prognostic significance of aneuploidy in iCCA patients after resection, the patients with aneuploid tumors may have a higher risk for tumor progression, especially during the first 3 years.
Assuntos
Adenoma/genética , Aneuploidia , Neoplasias dos Ductos Biliares/genética , Colangiocarcinoma/genética , DNA de Neoplasias/genética , Citometria de Fluxo , Hamartoma/genética , Adenoma/mortalidade , Adenoma/patologia , Adenoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Bases de Dados Factuais , Diagnóstico Diferencial , Progressão da Doença , Feminino , Hamartoma/mortalidade , Hamartoma/patologia , Hamartoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Fatores de TempoRESUMO
Until recently, 10% of hepatocellular adenomas (HCAs) remained unclassified (UHCA). Among the UHCAs, the sonic hedgehog HCA (shHCA) was defined by focal deletions that fuse the promoter of Inhibin beta E chain with GLI1. Prostaglandin D2 synthase was proposed as immunomarker. In parallel, our previous work using proteomic analysis showed that most UHCAs constitute a homogeneous subtype associated with overexpression of argininosuccinate synthase (ASS1). To clarify the use of ASS1 in the HCA classification and avoid misinterpretations of the immunohistochemical staining, the aims of this work were to study (1) the link between shHCA and ASS1 overexpression and (2) the clinical relevance of ASS1 overexpression for diagnosis. Molecular, proteomic, and immunohistochemical analyses were performed in UHCA cases of the Bordeaux series. The clinico-pathological features, including ASS1 immunohistochemical labeling, were analyzed on a large international series of 67 cases. ASS1 overexpression and the shHCA subgroup were superimposed in 15 cases studied by molecular analysis, establishing ASS1 overexpression as a hallmark of shHCA. Moreover, the ASS1 immunomarker was better than prostaglandin D2 synthase and only found positive in 7 of 22 shHCAs. Of the 67 UHCA cases, 58 (85.3%) overexpressed ASS1, four cases were ASS1 negative, and in five cases ASS1 was noncontributory. Proteomic analysis performed in the case of doubtful interpretation of ASS1 overexpression, especially on biopsies, can be a support to interpret such cases. ASS1 overexpression is a specific hallmark of shHCA known to be at high risk of bleeding. Therefore, ASS1 is an additional tool for HCA classification and clinical diagnosis.
RESUMO
Fibrolamellar hepatocellular carcinoma is a rare subtype of hepatocellular carcinoma with distinct clinical and histological features, and better survival compared with conventional hepatocellular carcinoma in some but not all series. We performed a comparative genomic hybridization analysis on 11 fibrolamellar carcinomas and correlated the findings with clinicopathologic features and survival. Chromosomal imbalances were identified in six cases (55%), whereas the other five (45%) yielded normal results. The mean number of aberrations per case was 3.9 for all cases and 7.2 in abnormal cases. Among the six abnormal cases, gains or losses were observed at 3 loci in two cases, 7 loci in one case, 8 loci in two cases and 14 loci in one case. The most common abnormalities were observed in chromosomes 7, 8 and 18, with 7q gain in five cases and 7p gain in four cases. Aberrations associated with intermediate or advanced conventional hepatocellular carcinomas, including losses at 3q, 4q and 13q were identified in 17-33% of fibrolamellar carcinomas. There was no correlation of chromosomal changes with age, gender and tumor size. The 5-year survival among the six patients with no chromosomal abnormalities was 80% (4/5) compared with 33% (2/6) in patients with chromosomal abnormalities (P=0.1). In conclusion, fibrolamellar carcinomas show fewer chromosomal abnormalities compared with those reported in literature for conventional hepatocellular carcinoma. The most common abnormalities occur in chromosomes 7 and 8. Fibrolamellar carcinomas with chromosomal changes appear to behave more aggressively compared with cases with no cytogenetic abnormalities. The favorable outcome in some fibrolamellar carcinomas may be due to absent or low number of cytogenetic aberrations.
Assuntos
Carcinoma Hepatocelular/genética , Hibridização Genômica Comparativa , Neoplasias Hepáticas/genética , Adolescente , Adulto , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Cromossomos Humanos Par 7/genética , Cromossomos Humanos Par 8/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS: To explore the utility of cytogenetic abnormalities in the distinction of hepatic adenoma (HA) and well-differentiated hepatocellular carcinoma (HCC). METHODS AND RESULTS: Array-based comparative genomic hybridization (CGH) was used to determine chromosomal abnormalities in 39 hepatocellular neoplasms: 12 HA, 15 atypical hepatocellular neoplasms (AHN) and 12 well-differentiated HCC. The designation of AHN was used in two situations: (i) adenoma-like neoplasms (n = 8) in male patients (any age) and women >50 years and <15 years old; (ii) adenoma-like neoplasms with focal atypical features (n = 7). CGH abnormalities were seen in none of the HAs (0/12), eight (53%) AHNs and 11 (92%) HCCs. The number and nature of abnormalities in AHN was similar to HCC with gains in 1q, 8q and 7q being the most common. Although follow-up information was limited, recurrence and/or metastasis were observed in three AHNs (two with abnormal, one with normal CGH). CONCLUSIONS: Adenoma-like neoplasms with focal atypical morphological features or unusual clinical settings such as male gender or women outside the 15-50 year age group can show chromosomal abnormalities similar to well-differentiated HCC. Even though these tumours morphologically mimic adenoma, they can recur and metastasize. Determination of chromosomal abnormalities can be useful in the diagnosis of AHN.
Assuntos
Adenoma de Células Hepáticas/diagnóstico , Carcinoma Hepatocelular/diagnóstico , Aberrações Cromossômicas , Hibridização Genômica Comparativa , Neoplasias Hepáticas/diagnóstico , Adenoma de Células Hepáticas/genética , Adenoma de Células Hepáticas/patologia , Distribuição por Idade , Fatores Etários , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Fatores SexuaisRESUMO
PURPOSE: To determine the frequency and histopathologic basis of hepatic surface nodularity at imaging in patients with fulminant hepatic failure. MATERIALS AND METHODS: The committee on human research approved this HIPAA-compliant study and waived written informed consent. Thirty-five consecutive patients [24 female [mean age, 38 years +/- 19 (standard deviation); range, 1-67 years] and 11 male [mean age, 29 years +/- 22; range, 2-61 years]] with a mean age of 35 years +/- 20 (range, 1-67 years) who underwent liver transplantation for fulminant hepatic failure at our institution during a 5-year period were retrospectively identified. Pretransplant ultrasonographic (n = 38; three patients each had two studies) and computed tomographic (n = 2) studies were retrospectively and independently reviewed for hepatic surface nodularity. Liver explant histopathologic findings (n = 33; slides unavailable in two patients) were reviewed for cirrhosis and for the combination of alternating foci of confluent regenerative nodules and necrosis. Differences among patients with nodular versus smooth liver surfaces in the proportion with the two histopathologic findings were compared with Fisher exact test. Differences in illness duration and maximum liver biochemical indices were compared with Mann-Whitney Rank Sum test. RESULTS: Fifteen of 35 patients (43%) demonstrated hepatic surface nodularity at pretransplant imaging, none of whom had cirrhosis at histopathologic examination. One patient with a smooth liver surface had cirrhosis. Compared with those who had a smooth liver surface, patients with hepatic surface nodularity had a significantly greater proportion with the histopathologic finding of a combination of alternating foci of confluent regenerative nodules and necrosis (12 of 14 vs one of 19, P < .001), longer illness duration (31 days +/- 32 vs 13 days +/- 13, P = .029), and lower maximum liver biochemical indices. CONCLUSION: Hepatic surface nodularity is commonly seen at imaging in fulminant hepatic failure and usually reflects a combination of alternating foci of confluent regenerative nodules and necrosis; this is important because an erroneous radiologic diagnosis of cirrhosis in this setting could adversely affect transplantation status.
Assuntos
Falência Hepática Aguda/patologia , Fígado/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Meios de Contraste , Feminino , Humanos , Lactente , Iohexol , Fígado/diagnóstico por imagem , Falência Hepática Aguda/diagnóstico por imagem , Falência Hepática Aguda/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
Glypican-3 is a heparin sulfate proteoglycan normally expressed in fetal liver and placenta, but not in normal adult liver. Preliminary studies have shown that glypican-3 can be useful for the diagnosis of hepatocellular carcinoma. We performed immunohistochemistry for glypican-3 on 80 resection cases of hepatocellular lesions to examine the utility of glypican-3 immunohistochemistry in hepatocellular carcinoma at two ends of the differentiation spectrum. Staining was compared to Hep Par 1 in poorly differentiated cases. Glypican-3 was expressed in 46 (79%) hepatocellular carcinomas (56, 83 and 89% of well, moderately and poorly differentiated respectively) and seven (64%) fibrolamellar carcinomas. Of the 16 well differentiated cases, 10 closely resembled adenoma and were diagnosed due to focal abnormalities and/or loss of reticulin. Glypican-3 expression was seen in 50% in this group. Hepatocellular carcinomas arising in cirrhotic liver were more likely to be glypican-3 positive (91 vs 57%, P=0.004). All hepatic adenomas and macroregenerative nodules were negative, and three (43%) high grade dysplastic nodules were positive. Focal staining was seen in regenerative nodules in four (11%) cirrhosis cases. Glypican-3 was significantly more sensitive than Hep Par 1 for diagnosis of poorly differentiated hepatocellular carcinomas (89 vs 63%, P=0.02). The difference was more significant when only cases with diffuse positive staining were considered (83 vs 21%, P<0.001). In conclusion, glypican-3 has high sensitivity for the diagnosis of hepatocellular carcinoma, but is less sensitive in the extremely well differentiated hepatocellular carcinoma and fibrolamellar variant of hepatocellular carcinoma. Caution should be exercised in using glypican-3 in biopsy specimens as cirrhotic nodules can show strong expression. Glypican-3 can be especially useful in the identification of poorly differentiated hepatocellular carcinoma as it has higher sensitivity compared to Hep Par 1.