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Granulomatous mastitis (GM), a benign inflammatory disease of the breast, often mimics breast cancer on presentation. We present a case of GM during pregnancy manifesting as a breast mass, sudden onset of plantar pain, and erythema nodosum (EN). A 31-year-old pregnant Japanese woman, gravida 2, para 1, was referred to our hospital with severe plantar pain on both soles, causing difficulty walking. This pain worsened and EN appeared on both lower legs, followed by a left breast mass. Ultrasound findings suggested malignancy; however, aspiration biopsy confirmed GM. Her arthritis and EN resolved 2 days after commencing oral prednisolone and her walking improved. EN with/without arthritis is commonly associated with GM, especially during pregnancy. The described manifestations with a breast mass are suggestive of this diagnosis.
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Breast papillary neoplasms include a wide range of tumor types, and their pathological diagnosis is sometimes difficult. Furthermore, the etiology of these lesions is still not fully understood. We report the case of a 72-years-old woman referred to our hospital with bloody discharge from the right nipple. An imaging study detected a cystic lesion, including a solid component contiguous with the mammary duct, in the subareolar region. The lesion was then removed by segmental mastectomy. Pathological examination of the resected specimen revealed an intraductal papilloma with atypical ductal hyperplasia. Moreover, the atypical ductal epithelial cells expressed neuroendocrine markers. The presence of an intraductal papillary lesion with neuroendocrine differentiation suggests solid papillary carcinoma. Thus, this case suggests that intraductal papilloma could be a precursor of solid papillary carcinoma.
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Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Carcinoma Papilar , Papiloma Intraductal , Feminino , Humanos , Idoso , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Papiloma Intraductal/diagnóstico por imagem , Papiloma Intraductal/cirurgia , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/cirurgia , Mastectomia , Diferenciação Celular , Hiperplasia/diagnóstico , Hiperplasia/cirurgiaRESUMO
AIMS: Ballooned hepatocytes represent liver cell degeneration and are histological hallmarks in the diagnosis of non-alcoholic steatohepatitis, a severe form of non-alcoholic fatty liver disease. However, the identification of ballooned hepatocytes is often difficult, especially in the clinical setting of patients with other chronic liver diseases. In this study, we investigated the utility of immunostaining for positive sonic hedgehog (SHh) protein and negative Keratin 8/18 (K8/18) expression on ballooned hepatocytes. METHODS AND RESULTS: Immunohistochemistry for SHh and K8/18 was evaluated independently by two experienced liver pathologists in non-tumorous liver tissue from 100 cases of resected hepatocellular carcinoma of various aetiology. The degree of hepatocyte ballooning was scored as follows: 0, none; 1, few; 2, many ballooned hepatocytes. These evaluations were performed using routine haematoxylin and eosin (H&E) staining, followed by immunostaining for SHh or K8/18. Using SHh or K8/18 immunostaining combined with H&E staining, the score of ballooned hepatocytes was upgraded in 20 and 19 cases, and downgraded in none and 2 cases, respectively. The percentage of observed agreement for ballooned hepatocytes scoring was 85% and 92%, and the weighted kappa value was 0.806 and 0.893 with SHh or K8/18 immunohistochemistry. Considering the immunohistochemistry results, background liver disease diagnosis was changed in 15 out of 100 cases (15%) evaluated. CONCLUSIONS: SHh and K8/18 immunohistochemistry are useful in detecting ballooned hepatocytes, regardless of background liver disease, and improving pathological diagnosis accuracy.
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Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Proteínas Hedgehog/metabolismo , Hepatócitos/patologia , Humanos , Imuno-Histoquímica , Queratina-18/metabolismo , Queratina-8/metabolismo , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismoRESUMO
We present a case of fetal atrioventricular block, heterotaxy, and ventricular noncompaction observed longitudinally from the first to early second trimesters using B-mode and Doppler imaging, including superb microvascular imaging. At 12 weeks of gestation, the atrial and ventricular rates were 133 and 67 beats/min, respectively, and dextrocardia was noted. At 15 weeks of gestation, detailed sonography revealed ventricular septal defect, interruption of the inferior vena cava, dilated azygos vein, and double-outlet right ventricle. In addition, superb microvascular imaging revealed irregular contours in the anatomical left ventricular wall, indicating prominent trabeculations of the ventricle, which were characteristic findings of ventricular noncompaction. At 21 weeks of gestation, intrauterine fetal death occurred, and the autopsy revealed complex congenital heart disease, including ventricular noncompaction.
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Bloqueio Atrioventricular , Comunicação Interventricular , Síndrome de Heterotaxia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Síndrome de Heterotaxia/complicações , Síndrome de Heterotaxia/diagnóstico por imagem , Humanos , Gravidez , Ultrassonografia Pré-Natal/métodosRESUMO
AIM: Cholangiolocellular carcinoma (CLC) is classified as a subtype of combined hepatocellular cholangiocarcinoma with stem-cell features (CHC-SC) in the latest World Health Organization classification. This subclassification of CHC-SCs is controversial and the relevance of such classification is unclear. METHODS: We analyzed a series of CHC-SCs and intrahepatic cholangiocarcinoma (iCCA) to clarify the clinicopathological features and mutational status of each tumor. RESULTS: Background liver disease, fibrosis stage, microvascular invasion, nodal metastasis, and IDH1/2 mutation status were associated with their histology. Compared with the intermediate cell subtype of CHC-SC (CHCs-SC-int), CLCs were less frequently associated with chronic viral hepatitis, and showed lower levels of serum alpha-fetoprotein. Compared with iCCAs, CLCs showed lower levels of serum carbohydrate antigen 19-9 (CA19-9) and a lower frequency of expression of S100P. Patients with iCCA showed worse overall survival than those with CLC or CHC-SC-int. In patients with iCCA, CLC, or CHC-SC-int, a histology of iCCA, microvascular invasion, and serum CA19-9 value of >100 U/mL were significant poor prognostic factors for overall survival in univariate analysis. Multivariate analysis showed that a high serum CA19-9 value was an independent poor prognostic factor for overall survival. CONCLUSIONS: Patients with CLC are likely to have a different etiology and mutational background from those with CHC-SC-int. Their clinicopathological manifestations are also different from those with classic iCCA. Our results suggest that CLC might be a distinct entity among primary liver carcinomas.
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AIM: Combined hepatocellular cholangiocarcinoma, subtype with stem-cell features, intermediate-cell subtype (INT) shows various histological appearances and could be misdiagnosed as intrahepatic cholangiocarcinoma (iCCA). In the present study, we aimed to identify specific histological diagnostic markers of INT. METHODS: We extracted RNA from FFPE sections of six INT, five iCCA, and five hepatocellular carcinoma (HCC) cases and compared gene expression between INT, iCCA, and HCC by microarray analysis. We then undertook immunohistochemical (IHC) staining of potential key molecules identified by microarray analysis, the conventional hepatocytic marker, hepatocyte paraffin (HepPar)-1, and the cholangiocytic markers, keratin (K) 7 and K19, on 35 INT, 25 iCCA, and 60 HCC cases. RESULTS: Microarray analysis suggested that malic enzyme 1 (ME1) was significantly upregulated in INT. Immunohistochemical analysis revealed that the positive rates of ME1 in INT, iCCA, and HCC were 77.1% (27/35), 28.0% (7/25), and 61.7% (37/60), respectively. Analysis of classification and regression trees based on IHC scores indicated that HepPar-1 could be a good candidate for discriminating HCC from the others with high sensitivity (93.3%) and high specificity (96.7%). A multiple logistic regression model and receiver operating characteristic curve analysis based on the IHC scores of ME1, K7, and K19 generated a composite score that can discriminate between INT and iCCA. Using this composite score, INT could be discriminated from iCCA with high sensitivity (88.6%) and high specificity (88.0%). CONCLUSIONS: We propose that ME1 is a useful diagnostic marker of INT when used in combination with other hepatocytic and cholangiocytic markers.
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BACKGROUND: Salivary duct carcinoma (SDC) is a rare tumor occurring in the salivary gland. SDC is a highly aggressive tumor and its prognosis is extremely poor. Effective treatments in advanced SDC have not yet been established. Recently, immune checkpoint inhibitors have paved the way for the treatment of various malignancies. We examined the expressions of programed death ligand (PD-L) 1/PD-L2 and programed death (PD-1), and the correlation of clinicopathological findings. METHODS: We examined 18 cases of SDC and conducted immunohistochemical staining using formalin-fixed paraffin-embedded full-face sections. RESULTS: The expression of PD-L1 and PD-L2 in tumor cells was observed in nine cases (50%) and 14 cases (78%), respectively. Cases with a high expression of PD-L1 and PD-L2 were found in four (22%) and seven cases (39%), respectively. The cases with a high expression of PD-L1 showed significantly shorter overall survival compared to those with low PD-L1 expression and null expression. We also examined the expression of PD-L1/PD-L2 and PD-1 of tumor-infiltrating mononuclear cells (TIMC) in stroma. The expressions of PD-L1 in tumor cells and stroma had a significant correlation. Association between the expressions of PD-L1 in tumor cells and those of PD-1 in stroma was significant. However, PD-L2 expression in the tumor had no significant correlation with expression in TIMCs. PD-L1, PD-L2 and PD-1 expressions in stroma were not associated with patient prognosis. CONCLUSIONS: High PD-L1 expression in SDC was strongly associated with unfavorable prognosis, indicating that PD-1/PD-L1 inhibitors could be effective in SDC.
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Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Expressão Gênica , Estudos de Associação Genética , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Ductos Salivares , Neoplasias das Glândulas Salivares/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteína 2 Ligante de Morte Celular Programada 1/genética , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Neoplasias das Glândulas Salivares/mortalidade , Taxa de SobrevidaRESUMO
AIM: Spleen stiffness is increased in liver cirrhosis (LC). We attempted to characterize the pathological features of spleen in LC. METHODS: We compared pathological findings of resected spleen tissues of 28 LC patients and those of six healthy controls. In addition, we measured spleen stiffness before splenectomy by shear wave elastography in nine LC patients. After splenectomy, we examined the relationship between spleen stiffness and pathological findings. RESULTS: Passive congestion of the spleen was more frequently observed in LC patients than in controls (P < 0.01). The sinus was wider in LC patients than in controls (P < 0.01). In the spleens of the LC patients, diffuse α-smooth muscle actin (αSMA) expression of sinusoidal mesenchymal cells and deposition of collagen fibers on the perisinusoidal wall were observed. In nine LC patients whose spleen stiffness was examined, the width of the sinus increased along with spleen stiffness (r = 0.89, P < 0.01). Spleen stiffness was higher in the spleen tissues with diffuse αSMA expression of sinusoidal mesenchymal cells than in those with partial αSMA expression of sinusoidal mesenchymal cells (P = 0.01). The degree of fibrosis was higher in the LC patients with diffuse αSMA expression of the red pulp than in those with partial αSMA expression of the red pulp (P = 0.03). CONCLUSION: In the LC patients, spleen tissues showed passive congestion with a dilated sinus, diffuse αSMA expression of sinusoidal mesenchymal cells, and deposition of collagen fibers on the perisinusoidal wall. This contributed to spleen stiffness.
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Insulinoma-associated protein 1 (INSM1) is an important biomarker of Achaete-scute homolog-like 1-driven pathways. For diagnosis of pancreatic neuroendocrine tumors (PanNET), chromogranin A (CGA), synaptophysin (SYP), and neural cell adhesion molecule (NCAM) were also considered as potential biomarkers. However, it is often difficult to diagnose it immunohistochemically. Hence, we examined the expression pattern of INSM1 in pancreatic solid tumors. We detected INSM1, CGA, SYP, and NCAM immunohistochemically, in 27 cases of NET [pure type: 25 cases, mixed adenoneuroendocrine carcinoma (MANEC): 2 cases]. We included 5 cases of solid-pseudopapillary neoplasm (SPN), 7 cases of acinar cell carcinoma (ACC), and 15 cases of pancreatic ductal adenocarcinoma (PDAC) as the control group. Nuclear expression of INSM1 was found in all PanNET pure type cases. However, expression of INSM1 was negative in PDAC, ACC, and SPN in all cases, whereas faint expression was seen in the cytoplasm from SPN. MANEC comprises of two components: neuroendocrine carcinoma and adenocarcinoma components. The NET component was positive for INSM1 expression, whereas the PDAC component does not express INSM1, which aids in distinguishing these components. Our results suggest that INSM1 is a useful immunohistochemical marker for diagnosing pancreatic neuroendocrine tumor.
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Biomarcadores Tumorais/genética , Carcinoma Neuroendócrino/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Proteínas Repressoras/genética , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Cromogranina A/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Moléculas de Adesão de Célula Nervosa/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Sinaptofisina/genéticaRESUMO
A 55-year-old man with rectal carcinoma underwent lower anterior resection. Eight years after surgery, multiple metastases were detected in the liver, lung, and abdominal lymph nodes. The metastatic cancers were resistant to standard chemotherapy. Thus, regorafenib was administered to the patient. The patient presented symptoms of Stevens-Johnson syndrome (SJS) nine days after regorafenib administration, and hence, treatment was terminated. To treat SJS, he received oral and topical steroid therapies. SJS is an important adverse event that hinders the continuation of regorafenib treatment. Thus, it is necessary to continually check the patient's skin condition carefully, especially at early stages of treatment. To our knowledge, this is the first report of SJS arising during the course of regorafenib treatment.
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Compostos de Fenilureia/efeitos adversos , Piridinas/efeitos adversos , Neoplasias Retais/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologia , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , RecidivaRESUMO
Hedgehog (Hh) signaling pathway dysregulation is involved in the pathogenesis of metabolic dysfunction-associated steatohepatitis, and the sonic Hh (SHh) protein, a pivotal molecule in the Hh pathway, is expressed in ballooned hepatocytes. The present study aimed to investigate the clinicopathological significance of SHh expression in steatohepatitic hepatocellular carcinoma (SH-HCC). Reverse transcription-quantitative polymerase chain reaction and immunohistochemistry were performed to examine SHh gene and SHh protein expression in SH-HCC. Additionally, patients with conventional HCC (C-HCC) were included in the control group. Comparisons of patient and tumor characteristics were also performed. The prevalence of SH-HCC was 3% in the whole cohort, and it was significantly associated with a high prevalence of diabetes mellitus. SHh mRNA was detected in all patients with SH-HCC, but not in 23% of patients with C-HCC. Notably, SHh mRNA expression was not significantly different between patients with SH-HCC and those with C-HCC; however, high SHh protein expression was significantly more frequent in SH-HCC patients than in those with C-HCC. Although the prognosis was not significantly different between the SH-HCC and C-HCC groups, high SHh protein expression was an independent poor prognostic factor for HCC. In conclusion, SHh could potentially serve as a therapeutic target for patients with HCC.
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BACKGROUND/AIM: Recently, vessels encapsulating tumor clusters (VETC) pattern and macrotrabecular massive (MTM) pattern of hepatocellular carcinoma (HCC) have been reported as aggressive histological types. These histological patterns showed an immunosuppressive tumor immune microenvironment (TIME). Since there have been no reports on the differences of these two subtypes simultaneously, this study examined the immunophenotypes and TIME of MTM-HCC and VETC-HCC immunohistochemically. PATIENTS AND METHODS: Seventy-four cases of previously diagnosed HCC, including 32 MTM-HCCs, 21 VETC-HCCs, and 21 conventional HCCs, were enrolled in immunohistochemical analysis. We conducted immunohistochemical analysis. RESULTS: We found that MTM-HCC showed less frequent expression of HepPar-1, which is one of the most common hepatocytic markers. In MTM-HCC, the frequency of high expression levels of Keratin19, carbonic anhydrase (CA) IX, and PD-L1 was higher compared to VETC-HCC and conventional HCC. PD-L1 expression was found in 34.4% of MTM-HCC, 0% of VETC-HCC, and 19.0% of conventional HCC. The rate of PD-L1 expression in MTM-HCC was significantly higher than the others (p=0.0015). PD-L1 expression was significantly associated with epithelial cell adhesion molecules and CA IX expression, which are representative markers of tumor stemness and hypoxic conditions, respectively. The CD8 infiltration in VETC-HCC was significantly lower than that in conventional HCC. CONCLUSION: MTM-HCC had different immunophenotypes and TIMEs compared to HCC with the VETC pattern. Although both had immunosuppressive TIME, the elements forming TIME were quite different. To enhance the immune checkpoint inhibitor efficacy, changing TIME from a suppressive to an active form is essential.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Antígeno B7-H1 , Estudos Retrospectivos , Microambiente TumoralRESUMO
There have been several investigations of non-mass-like (NML) lesions on ultrasound (US) since Uematsu first described this approach, and it is a relatively new concept for breast examination. However, the results have varied, and there have been only a few studies related to the detailed histopathology of NML lesions on US. Here, we review the histopathology of NML lesions. NML lesions are pathologically benign, atypical, or malignant. There are two major findings of NML lesions on US: architectural distortion and calcifications. Architectural distortion pathologically indicates a fibrous change with ductal proliferation, invasive breast carcinoma, and carcinoma in situ. Histopathologically, microcalcifications are seen in both benign and malignant lesions, and it is important to distinguish between these lesions among NML lesions, particularly fibrocystic changes including adenosis and hyperplasia in the case of benign lesions and carcinoma in situ (ductal and lobular) in the case of malignant lesions. The differential major points may be whether NML lesions are associated with abundant hyperechoic foci, which indicate comedo necrosis on histology. They are usually high-grade carcinoma in situ that may be positive for HER2 or triple negativity. A recent report indicated that low-grade carcinoma in situ showed better survival than higher-grade carcinoma in situ, which is often accompanied by comedo necrosis on histology, reflecting visible microcalcification on US. NML lesions are considered to include a certain rate of low-grade carcinoma in situ. Therefore, more caution may be needed when detecting and managing NML lesions to avoid overdiagnosis and overtreatment as a result of this recent "low-risk ductal carcinoma in situ" concept.
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Neoplasias da Mama , Calcinose , Carcinoma in Situ , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma in Situ/patologia , Calcinose/diagnóstico por imagem , Fibrose , Hiperplasia/patologia , Necrose/patologiaRESUMO
Mitochondrial diseases are a heterogeneous group of genetic disorders caused by pathogenic variants in genes encoding gene products that regulate mitochondrial function. These genes are located either in the mitochondrial or in the nuclear genome. The TOMM7 gene encodes a regulatory subunit of the translocase of outer mitochondrial membrane (TOM) complex that plays an essential role in translocation of nuclear-encoded mitochondrial proteins into mitochondria. We report an individual with a homozygous variant in TOMM7 (c.73T>C, p.Trp25Arg) that presented with a syndromic short stature, skeletal abnormalities, muscle hypotonia, microvesicular liver steatosis, and developmental delay. Analysis of mouse models strongly suggested that the identified variant is hypomorphic because mice homozygous for this variant showed a milder phenotype than those with homozygous Tomm7 deletion. These Tomm7 mutant mice show pathological changes consistent with mitochondrial dysfunction, including growth defects, severe lipoatrophy, and lipid accumulation in the liver. These mice die prematurely following a rapidly progressive weight loss during the last week of their lives. Tomm7 deficiency causes a unique alteration in mitochondrial function; despite the bioenergetic deficiency, mutant cells show increased oxygen consumption with normal responses to electron transport chain (ETC) inhibitors, suggesting that Tomm7 deficiency leads to an uncoupling between oxidation and ATP synthesis without impairing the function of the tricarboxylic cycle metabolism or ETC. This study presents evidence that a hypomorphic variant in one of the genes encoding a subunit of the TOM complex causes mitochondrial disease.
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Doenças Mitocondriais , Membranas Mitocondriais , Camundongos , Animais , Membranas Mitocondriais/metabolismo , Proteínas de Transporte/metabolismo , Mitocôndrias/genética , Doenças Mitocondriais/genética , Proteínas do Complexo de Importação de Proteína Precursora MitocondrialRESUMO
Lymphocyte-rich hepatocellular carcinoma (LR-HCC), a newly proposed subtype of HCC, is characterized with abundant lymphocyte infiltration in the tumor. LR-HCC has a relatively good prognosis and is quite rare (<1% of all HCC). We examined LR-HCC clinicopathological and molecular characteristics by analyzing 451 surgically resected HCC cases without any prior treatment history at our hospital between 2012 and 2021. Clinicopathological features of LR-HCC and other HCCs (non-LR-HCC) were compared. Neoplastic and nonneoplastic hepatocytes from LR-HCC (n = 4) were collected with a laser microdissection system; RNA was extracted, followed by microarray analysis to examine lymphocytic infiltration-related molecular targets. Immunohistochemical staining of identified molecular target was performed in LR-HCC and non-LR-HCC. CD3, CD20, and CD8 immunostaining was also performed in LR-HCCs. There were 28 cases of LR-HCC (6%). No statistically significant differences were found in clinicopathological features, except for gross type, between LR-HCC and non-LR-HCC cases. The LR-HCC 5-year survival rate was >90%. Microarray analysis revealed high CCL20 expression in LR-HCC cases; immunohistochemical study showed significantly higher CCL20 expression in LR-HCC (P < 0.01) than in non-LR-HCC. CCR6, the only CCL20 receptor, was observed in infiltrating lymphocytes and HCC cells in LR-HCC. There were significantly more CD3-positive cells than CD20-positive cells (P < 0.0001) in tumor-infiltrating lymphocytes, most of which were CD8-positive T cells. In conclusion, there were no significant differences in clinicopathological characteristics between LR-HCC and non-LR-HCC, except for gross and LR microscopic features. CCL20 expression in LR-HCC may contribute to infiltration of large numbers of CD8-positive lymphocytes.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologiaRESUMO
BACKGROUND: Few reports of benign recurrent intrahepatic cholestasis (BRIC) have focused on East Asian patients. We describe the clinicopathologic features, genetics, treatment, and outcomes in Japanese BRIC patients. METHODS: We recruited patients with BRIC type 1 (BRIC-1) or 2 (BRIC-2) treated at four pediatric centers and one adult center between April 2007 and March 2022. Demographics, clinical course, laboratory results, molecular genetic findings concerning ATP8B1 and ABCB11 genes, histopathology, and treatment response were examined retrospectively. RESULTS: Seven Japanese patients with BRIC were enrolled (four male, three female; four BRIC-1 and three BRIC-2). The median age at onset for BRIC-1 was 12 years; for BRIC-2, it was 1 month. Intermittent cholestatic attacks numbered from one to eight during the 11 years of median follow-up. Six patients received a mainstream education; only one patient attended special education. None developed cirrhosis. Three with BRIC-1 showed compound heterozygosity for a variant ATP8B1 gene, while one was heterozygous; two BRIC-2 patients showed compound heterozygosity in ABCB11 and one was heterozygous. Liver biopsy specimens obtained during cholestatic attacks showed fibrosis varying from none to moderate; inflammation was absent or mild. Rifampicin administered to three patients for cholestatic attacks was effective in all, as was cholestyramine in two of three. CONCLUSIONS: To our knowledge, this is the first East Asian multicenter study of BRIC patients. Onset age and number of cholestatic attacks varied. Rifampicin and cholestyramine were effective against attacks. No patient developed cirrhosis; most had normal growth and development. The long-term outcomes were satisfactory.
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Benign recurrent intrahepatic cholestasis type 1 (BRIC1) is a rare autosomal recessive disorder that is characterized by intermittent episodes of jaundice and intense pruritus and caused by pathogenic variants of adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1). The presence of genetic heterogeneity in the variants of ATP8B1 is suggested. Herein, we describe a unique clinical course in a patient with BRIC1 and a novel heterozygous pathogenic variant of ATP8B1. A 20-year-old Japanese man experienced his first cholestasis attack secondary to elevated transaminase at 17 years of age. Laboratory examinations showed no evidence of liver injury caused by viral, autoimmune, or inborn or acquired metabolic etiologies. Since the patient also had elevated transaminase and hypoalbuminemia, he was treated with ursodeoxycholic acid and prednisolone. However, these treatments did not relieve his symptoms. Histopathological assessment revealed marked cholestasis in the hepatocytes, Kupffer cells, and bile canaliculi, as well as a well-preserved intralobular bile duct arrangement and strongly expressed bile salt export pump at the canalicular membrane. Targeted next-generation sequencing detected a novel heterozygous pathogenic variant of ATP8B1 (c.1429 + 2T > G). Taken together, the patient was highly suspected of having BRIC1. Ultimately, treatment with 450 mg/day of rifampicin rapidly relieved his symptoms and shortened the symptomatic period.
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BACKGROUND: Hepatocellular carcinoma (HCC) shows a high mortality rate. A macrotrabecular (MT) pattern and vessels encapsulating tumor clusters (VETC) pattern have been reported as aggressive histological patterns in HCC. However, their cut-off values have been contentious. METHOD: Nine hundred eighty-five cases of previously diagnosed HCC were enrolled. The percentage areas of the MT and/or VETC pattern with ≥ 5% at every 10% increment were assessed. Clinicopathological analysis including patients' prognosis was conducted. RESULT: One hundred fifty-eight and eighty-four cases were accompanied by 5-49% and ≥ 50% MT components, respectively. Two hundred six and twenty-nine cases had 5-49% and ≥ 50% VETC components, respectively. Cases with these histological patterns in common had aggressive characteristics and worse prognosis compared to cases with none of these patterns. The presence of 5-49% VETC pattern was independent worse prognostic factor in overall survival (P = 0.046). HCCs with the MT pattern and the VETC pattern were significantly accompanied by the VETC pattern and the MT pattern (P < 0.001), respectively. CONCLUSION: As even 5% of the MT pattern and/or VETC pattern affected the prognosis of patients with HCC, the amount of these pattern should be described in pathological reports. This information could be useful in expecting patients' prognosis and providing proper post-operative treatments.
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Although new ultrasound (US) methods able to quantitatively assess liver fat content have been recently developed, B-mode US is still the major method for detecting liver steatosis during medical checkups. However, some pathological cases yield false-positive or false-negative liver steatosis results using B-mode US. In addition, histologically, the degree of fat deposits and the size of fat droplets in the liver can affect the sensitivity and specificity of the diagnosis of liver steatosis using B-mode US. As B-mode US evaluation of fatty liver relies on operator expertise, the operator should be aware that there are some cases of liver steatosis that are difficult to evaluate with B-mode US. Here, we describe the pathological findings of liver steatosis that is difficult to evaluate with US.
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Fígado Gorduroso , Fígado Gorduroso/diagnóstico por imagem , Humanos , Fígado/diagnóstico por imagem , Sensibilidade e Especificidade , UltrassonografiaRESUMO
BACKGROUND/AIM: Hepatocellular carcinoma (HCC) remains one of the biggest medical issues. Pigment epithelial-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors. PEDF interacts with its two receptors, adipose triglyceride lipase (ATGL) and laminin receptor (LR). MATERIALS AND METHODS: We conducted immunohistochemical staining for PEDF, LR and ATGL in 151 resected HCCs and their background liver tissues. RESULTS: High expression of LR in HCC was associated with high histological grade and portal vein invasion, while high expression of PEDF in HCC was associated with absence of portal vein invasion. High LR expression in background liver was statistically associated with low serum albumin levels and was an independent prognostic factor of worse outcomes. No cases with more than 5% fatty degeneration in the background liver tissue showed high PEDF expression. CONCLUSION: PEDF/LR/ATGL could be potential biomarkers in HCC and various chronic hepatic disorders.