A scoring system for the diagnosis of non-alcoholic steatohepatitis from liver biopsy

Background@#Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis. @*Methods@#Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses (‘not-NASH,’ ‘borderline,’ and ‘NASH’) of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system. @*Results@#Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52–0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH. @*Conclusions@#A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.

Microscopic Findings of Malassezia Colonization in Seborrheic Dermaititis / 대한의진균학회지

No abstract available.

Interobserver Agreement on Pathologic Features of Liver Biopsy Tissue in Patients with Nonalcoholic Fatty Liver Disease

BACKGROUND: The histomorphologic criteria for the pathological features of liver tissue from patients with non-alcoholic fatty liver disease (NAFLD) remain subjective, causing confusion among pathologists and clinicians. In this report, we studied interobserver agreement of NAFLD pathologic features and analyzed causes of disagreement. METHODS: Thirty-one cases of clinicopathologically diagnosed NAFLD from 10 hospitals were selected. One hematoxylin and eosin and one Masson's trichrome-stained virtual slide from each case were blindly reviewed with regard to 12 histological parameters by 13 pathologists in a gastrointestinal study group of the Korean Society of Pathologists. After the first review, we analyzed the causes of disagreement and defined detailed morphological criteria. The glass slides from each case were reviewed a second time after a consensus meeting. The degree of interobserver agreement was determined by multi-rater kappa statistics. RESULTS: Kappa values of the first review ranged from 0.0091-0.7618. Acidophilic bodies (k = 0.7618) and portal inflammation (k = 0.5914) showed high levels of agreement, whereas microgranuloma (k = 0.0984) and microvesicular fatty change (k = 0.0091) showed low levels of agreement. After the second review, the kappa values of the four major pathological features increased from 0.3830 to 0.5638 for steatosis grade, from 0.1398 to 0.2815 for lobular inflammation, from 0.1923 to 0.3362 for ballooning degeneration, and from 0.3303 to 0.4664 for fibrosis. CONCLUSIONS: More detailed histomorphological criteria must be defined for correct diagnosis and high interobserver agreement of NAFLD.

A Case of Malignant Melanoma with Zosteriform Skin Metastasis Arising in a Medium-sized Congenital Melanocytic Nevus / 대한피부과학회지

Zosteriform metastasis from malignant melanoma is a rare type of skin metastasis that shows cutaneous lesions including patches, plaques, and nodules along with dermatomes, and thus needs to be distinguished from herpes zoster skin infection. Although some authors have explained the mechanism of zosteriform metastasis, its pathogenesis remains unknown. Herein, we describe an 85-year-old woman with zosteriform metastasis of malignant melanoma arising in a medium-sized congenital melanocytic nevus.

Atypical teratoid rhabdoid brain tumor in an infant with ring chromosome 22 / 소아과

Reports of constitutional ring chromosome 22, r(22) are rare. Individuals with r(22) present similar features as those with the 22q13 deletion syndrome. The instability in the ring chromosome contributes to the development of variable phenotypes. Central nervous system (CNS) atypical teratoid rhabdoid tumors (ATRTs) are rare, highly malignant tumors, primarily occurring in young children below 3 years of age. The majority of ATRT cases display genetic alterations of SMARCB1 (INI1/hSNF5), a tumor suppressor gene located on 22q11.2. The coexistence of a CNS ATRT in a child with a r(22) is rare. We present a case of a 4-month-old boy with 46,XY,r(22)(p13q13.3), generalized hypotonia and delayed development. High-resolution microarray analysis revealed a 3.5-Mb deletion at 22q13.31q13.33. At 11 months, the patient had an ATRT (5.6 cmx5.0 cmx7.6 cm) in the cerebellar vermis, which was detected in the brain via magnetic resonance imaging.

Basal Cell Carcinoma of the Umbilicus / 대한피부과학회지

Basal cell carcinoma (BCC) is the most common skin cancer in humans. It usually develops on sun-exposed areas of the head and neck but can occur anywhere on the body. The various clinical features include nodules, ulcers, bleeding, crust, or scale. Thus, it is important to distinguish BCC from other diseases with similar clinical features. The umbilicus is one of the sun-protected sites where BCC rarely develops. Herein, we describe 71-year-old woman with umbilical BCC initially misdiagnosed as pyoderma.

Congenital Melanocytic Nevus Combined with Cystic Change due to Recurrent Folliculitis / 대한피부과학회지

Nevus with cyst is defined as a single lesion in which there is the coexistence of an epidermoid cyst and a melanocytic nevus. Similar clinical and histopathologic changes can be observed when a hair follicle ruptures and subsequent folliculitis with supprative granulomatous reaction occurs beneath a melanocytic nevus. This cystic change due to inflammation is a different pathologic phenomenon from the formation of an epidermal cyst. Hence, it is necessary to differentiate between these two conditions. We report here on a case of congenital melanocytic nevus combined with cystic change due to inflammation in a 39-year-old man.

Current Trends in the Epidemiological and Pathological Characteristics of Gastrointestinal Stromal Tumors in Korea, 2003-2004

Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies.

Immunohistochemical Study about the Origin of Bile Ductules Proliferation in Obstructive Liver Disease

BACKGROUND: The relationship between bile duct proliferation and portal fibrosis in obstructive liver diseases remains unclear. The purpose of this study is to analyze the relationship between hepatic stellate cells (HSC), hepatocytes and bile ductule proliferation in obstructive liver disease using immunoreactivity for alpha-SMA (alpha-smooth muscle actin), CK7, and CK19. METHODS: We used 20 human tissue samples with hepatic fibrosis due to intrahepatic stones and liver cirrhosis. Immunohistochemical staining was performed using the streptavidin-biotin method. RESULTS: Proliferations of bile ductules at the periphery of the hepatic lobules, and diffuse HSC activation in the perisinusoidal spaces were observed in all cases. Immunoreactivity of the hepatocytes for CK7 and CK19 suggested a possible phenotypic transformation into bile duct epithelium during fibrogenesis. Immunohistochemical-analyses of alpha-SMA expression profiles showed that intralobular HSCs and some hepatocytes underwent early phenotypic changes, and that the accumulation of collagen coincides with that of alpha-SMA-labeled myofibroblasts around portal/septal ductular structures. CONCLUSIONS: Our results showed the possibility of a phenotypic transformation of hepatocytes into bile ductular epithelium. It is suggested that hepatocytes might play a role in bile ductule proliferation in obstructive liver disease.

A case of glycogen storage disease type Ib / 소아과

We report a case of an 18-month-old girl with glycogen storage disease type Ib (GSD Ib). Her neutrophil counts had gradually decreased to less than 500/microL by the age of 3 years. However, there were no recurrent bacterial infections. Mutation analysis of the glucose-6-phosphate translocase (G6PT) gene revealed a compound heterozygous missense mutation (Ala148Val/Gly273Asp).

Transcriptional Regulation of Hepatic Stellate Cell Activation by siRNA for TGF-beta1

BACKGROUND: The cytokine-induced activation of hepatic stellate cells (HSC) plays a major role in liver fibrosis. Quiescent HSCs undergo phenotypic transformation called "transdifferentiation" in response to viral, chemical or immune insults to the liver. The cytokine TGF-beta1 plays a key role in progressive liver fibrosis. Since small interfering RNA (siRNA) is a powerful tool for silencing gene expression post-transcriptionally, the present study aimed to determine whether synthetic TGF-beta1 siRNA down-regulates the expression of the TGF-beta1 gene in immortalized and activated rat HSCs (HSC-T6s). The study examined whether synthetic TGF-beta1 siRNA prevents rat HSCs activation and extracellular matrix (ECM) production. METHODS: TGF-beta1 siRNA or a control (pU6) siRNA was added to HSC-T6 culture media. We then performed RT-PCR and western blot analyses for TGF-beta1 and ECM components (fibronectin, type-I collagen, and TIMP-1). RESULTS: TGF-beta1 siRNA significantly down-regulated expression of TGF-beta1 mRNA and protein and attenuated mRNA and protein expressions of type-I collagen, fibronectin, and TIMP-1, as compared to the control. CONCLUSIONS: TGF-beta1 siRNA can effectively down-regulate the expression of TGF-beta1 in rat HSC, resulting in significant inhibition of HSC activation and of ECM production. These data indicate that synthetic TGF-beta1 siRNA can be a useful treatment modality to prevent liver fibrosis.

Effect of Combination of Anticancer Agents and Nitroimidazoles on the Survival of Human Hepatocellular Carcinoma Cells under Hypoxic Conditions

PURPOSE: In a previous study, we have shown that anticancer agents inhibiting topoisomerases improve survival of tumor cells under hypoxic condition. In the present study, we evaluated whether and how cell survival effect of the anticancer agents under hypoxic conditions could be eliminated by the addition of nitroimidazoles, a class of bioreductive agents. METHODS: Human hepatocellular carcinoma cells (HepG2) were incubated with different combinations of pimonidazole (1~1,000 microg/ml) and doxorubicin (0.1 or 1 microg/ml) concentrations under different O2 concentrations [1, 3, 5, 10 and 21 O2]. Then cell numbers, glucose concentrations and lactic acid concentrations in the medium were measured, and DNA fragmentation assay was performed. Finally, different combinations of nitroimidazoles, such as pimonidazole, misonidazole, etanidazole, tinidazole, metronidazole, ornidazole or dimetridazole, and anticancer agents, such as doxorubicin, campothecin, epirubicin, dactinomycin, etoposide or mitomycin C was added to the cell culture medium under hypoxic conditions (1% O2). RESULTS: Pimonidazole at a concentration of 100 microg/ml eliminated cell survival effect of doxorubicin at the concentrations of 0.1 and 1 microg/ml under hypoxic condition (1% O2) by promoting apoptosis. Almost all the cells died even after 24 hours of incubation for all the oxygen concentrations at a combination of 100 microg/ml pimonidazole and 1 microg/ml doxorubicin. Finally, pimonidazole at a concentration of 100 microg/ml, and misonidazole or etanidazole at a concentration of 1,000 microg/ml eliminated cell survival effect of all the anticancer agents tested under hypoxic condition. CONCLUSION: Combination therapy of doxorubicin (adriamycin) with pimonidazole can maximize dororubicin efficacy by eliminating cell survival effect of doxorubicin under hypoxic conditions in treating solid tumors, such as breast cancer.

Two Cases of Conjunctival Mucosa-associated Lymphoid Tissue (MALT) Lymphomas Treated by Cryotherapy

PURPOSE: To report two cases of conjunctival mucosa-associated lymphoid tissue (MALT) lymphomas treated with cryotherapy. CASE SUMMARY: Two patients with MALT lymphoma of the conjunctiva were treated by carbon dioxide cryotherapy under topical anesthesia using 0.5% proparacaine hydrochloride (Alcaine(R), Alcon). Cryotherapy was repeated in recurrent lesions up to three times. One patient was free of the tumor for 18 months of follow-up after the third cryotherapy was performed. The second patient had complete disease arrest for 9 months after the third cryotherapy. Neither patient experienced complications during the follow-up period. CONCLUSIONS: Cryotherapy is a comparatively easy treatment tool with fewer complications for patients, making it preferable from a patient's perspective as well. Cryotherapy may be a useful treatment modality in patients with MALT lymphomas localized to the conjunctiva.

Primary Hepatic Carcinoid Tumor Detected Incidentally in Patient with Recurrent Peptic Ulcer Perforation

The liver is a common site for carcinoid metastases, and primary hepatic carcinoid tumor (PHCT) is a very rare entity. The diagnosis of PHCT is principally based on the histopathological confirmation of carcinoid tumor and the exclusion of a nonhepatic primary tumor. A 45-year-old man who presented with an intraabdominal abscess caused by recurrent peptic ulcer perforation had a huge heterogeneous mass in the central portion of the liver. The preoperative impression was peripheral cholangiocellular carcinoma. Central bisectionectomy was performed together with difficult adhesiolysis. On surgical exploration, there were no extrahepatic lesions. The postoperative course was uneventful, except for biloma formation, and the pathologic biopsy result was carcinoid tumor with positive immunohistochemical staining for chromogranin A. Our patient has been free of symptoms, including peptic ulcer, and there have been no abnormal findings on the follow-up abdominal images for 1 year. Accordingly, the diagnosis was primary hepatic carcinoid. In conclusion, PHCT should be diagnosed by the absence of extrahepatic lesion on surgical exploration and follow up throughout the clinical and imaging studies. A preoperative suspicion of PHCT is significant for conducting clinical investigations of a tumor's characteristics.

Bullous Eosinophilic Cellulitis (Wells' Syndrome) in a Patient with Churg-Strauss Syndrome: A Case Report and Review of Literatures / 대한류마티스학회지

Wells' syndrome is an inflammatory dermatosis with associated aberrant eosinophil responses caused by unknown factors. Its histology is characterized by erythematous plaques with "flame figures" in the dermis, which is potentially diagnostic but not pathognomic. Cases of Wells' syndrome in patients with Churg-Strauss syndrome (CSS), which is characterized by antineutrophil cytoplasmic antibody-related necrotizing vasculitis, marked peripheral eosinophilia, and eosinophil tissue infiltrates, have rarely been reported, and the pathogenic association between these two diseases remains undetermined. Differences of clinical and histopathologic features of these two diseases suggest that they are distinct disease entities, even though, in part, they share pathogenic mechanisms. Here we present a new case with Wells' syndrome in a patient with CSS, treated with systemic steroid.

A Case of Lobular Panniculitis in Dermatomyositis Patient / 대한류마티스학회지

Panniculitis is an inflammation of subcutaneous fat tissue, and found in variety of clinical setting, like erythema nodosum, lupus or other connective tissue diseases. Panniculitis, as a clinical feature of dermatomyositis, is rare and should be included in one of the sign to be differentiated. We present a 77-year-old female dermatomyositis patient who showed a clinically and histologically evident lobular panniculitis, and successfully treated with oral prednisolone.

The Histological Change of Orbicularis Oculi Muscle according to the Age

This study is to investigate the patients who had blepharoplasty for cosmetic purposes or facial nerve disorders. 21 patients were examined with an age from 17 to 63 years. Sixteen cases were classified as a normal group for investigation of the histopathologic change according to the age. The rest were patients of Bell's palsy(2), Botox(R) injection(2) and blepharospasm (1). We measured a mean diameter of myofiber and dimension's proportion of muscluar tissue per regular visual field. First, we measured a statistical significance according to the age in normal cases by grouping them into younger than 30-year-old, 30's, 40's, 50's and 60's. Second, we divided normal cases(16) into Group A and B by two bases for statistical analysis. In conclusion, although there were several differences as vacuolation, internalization of sarcolemnic nuclei between 35-year-old and 62-year-old patients in simple comparison, there was no uniform decrease according to the age. There were also no significant statistical changes in the value of a diameter of myofibers and dimension's proportion of muscular tissue according to the age in any of the two normal groups. But in Botox(R) injection and Bell's palsy, blepharospasm patients, two values showed remarkable difference compared to the normal group of same age.

A Case of Primary Adenosquamous Carcinoma of the Liver with Formation of Colonic Fistula / 대한소화기학회지

Primary adenosquamous carcinoma of the liver is generally considered as an extremely rare subtype of cholangiocarcinoma. It has been reported mostly in a form of case studies. As far as we know, there was only one case report on tumor related with biliary fistula. Recently, we experienced a case of primary adenosquamous carcinoma of liver with a formation of tumor-colonic fistula. A 54-year-old man was transferred to our hospital due to liver mass detected by abdominal ultrasonogram. Dynamic computed tomogram of liver showed a large irregular hypodense mass without rim enhancement in right lobe of liver and also suggested a fistula formation between the tumor and hepatic flexure of right colon. Colonoscopic examination showed a large colonic wall defect in hepatic flexure and a friable, nodular mucosa around the defected colonic wall. Extended right lobectomy and right hemicolectomy were done. Microscopically, the tumor was composed of squamous cell carcinoma mainly with foci of the adenocarcinoma component.

Effect of Antibiotics on the Survival of Human Hepatocellular Carcinoma Cells under Hypoxic Conditions

PURPOSE: Antibiotics that kill or suppress the growth of bacteria also affect tumors directly or indirectly. The authors aimed to show whether some antibiotics can improve cancer cell survival under hypoxic conditions, and how the antibiotics improve the cells under hypoxic conditions. METHODS: Human hepatocellular carcinoma cells (HepG2) were grown at 1% oxygen concentration. Cell numbers, glucose concentrations and lactic acid concentrations in the medium were measured at different incubation times, in the absence or presence of aminoglycosides, tetracyclines, quinolones, penicillins, cephalosporins, sulfonamides, or chloramphenicols. DNA fragmentation assay was performed to study the mechanism how some antibiotics improve the cell survival under hypoxic conditions. RESULTS: Of the antibiotics tested, only aminoglycosides, tetracyclines, quinolones and the chloramphenicol improved cell survival under hypoxic conditions. Geneticin (G418), an aminoglycoside chosen as an example, improved cell survival even if glucose in the medium was completely consumed. At the same time, the appearance of DNA ladder was delayed in the presence of geneticin, which was also the same for the other antibiotics that improved cell survival under hypoxic conditions. CONCLUSION: Some antibiotics improved hepatocellular carcinoma cells under ischemic conditions by inhibiting apoptosis. The results implies that the antibiotics might adversely affect solid tumors, by improving cancer cell growth where hypoxic or ischemic conditions occur in the core region. Therefore, we might be cautious in choosing antibiotics for cancer patients with solid tumors, especially when the patients should be treated with antibiotics for a long time.

Gastrointestinal Stromal Tumors in Koreans: It's Incidence and the Clinical, Pathologic and Immunohistochemical Findings

Seven hundred forty seven cases of gastrointestinal stromal tumors (GISTs) in Koreans who were diagnosed between 2001 and 2002 were analyzed to evaluate their occurrence and their clinical, pathologic and immunohistochemical findings. The most frequent location of tumor was in the stomach (63%), followed by the small intestine (30%), the colorectum (5%), and the esophagus (2%). c-kit expression was found in 93.6% of the cases, while CD34, SMA and S-100 protein was positive in 80.1%, 28.2%, and 20.2%, respectively. c-kit positivity was high in the stomach (94.2%) and small intestine (94.6%), while it was relatively low in the colorectum (85.0%), and esophagus (81.2%). The positivity for CD34 was correlated with the higher risk of GISTs (p=0.04). Follow up of the patients showed that 58 primary GISTs patients died and 20 of these patients were recurrent or metastatic at the time of diagnosis. The pathologic diagnosis to predict the risk of aggressive behavior of GISTs was correlated with the numbers of tumor, clinical stage, epithelioid histologic type, cellularity, cellular atypia, necrosis, and mucosal invasion (p= 0.00). GISTs with a poor prognosis were closely related to the clinical stage at presentation, the locations of the tumor, and the ages of the patients.