Hepatocellular adenoma (HCA) is a heterogeneous entity, from both the histomorphological and molecular aspects, and the resultant subclassification has brought a strong translational impact for both pathologists and clinicians. In this review, we provide an overview of the recent updates on HCA from the pathologists’ perspective and discuss several practical issues and pitfalls that may be useful for diagnostic practice.
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Background There is increasing interest in hepatocellular carcinomas (HCC) expressing “stemness”-related markers, as they have been associated with aggressive behavior and poor prognosis. In this study, we investigated the usefulness of Sal-like protein 4 (SALL4), a recently proposed candidate marker of “stemness.” Methods: Immunohistochemical stains were performed for SALL4, K19, and epithelial cellular adhesion molecule (EpCAM) on tissue microarrays constructed from 190 surgically resected HCCs, and the results were correlated with the clinicopathological features and patient survival data. Results: Nuclear SALL4 expression was observed in 39/190 HCCs (20.5%), while K19 and EpCAM were expressed in 30 (15.9%) and 92 (48.7%) HCCs, respectively. The nuclear expression was generally weak, punctate or clumped. SALL4 expression was significantly associated with a poor overall survival compared to SALL4-negative HCCs (p = .014) compared to SALL4-negative HCCs. On multivariate analysis adjusted for tumor size, multiplicity, vascular invasion, and pathological tumor stage, SALL4 remained as a significant independent predictor of decreased overall survival (p= .004). SALL4 expression was positively correlated with EpCAM expression (p = .013) but not with K19 expression. HCCs that expressed both SALL4 and EpCAM were associated with significantly decreased overall survival, compared to those cases which were negative for both of these markers (p = .031). Conclusions: Although SALL4 expression was not significantly correlated with other clinicopathological parameters suggestive of tumor aggressiveness, SALL4 expression was an independent predictor of poor overall survival in human HCCs, and was also positively correlated with EpCAM expression.
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DNA demethylation induces SALL4 gene re-expression in subgroups of hepatocellular carcinoma associated with Hepatitis B or C virus infection H Fan, Z Cui, H Zhang, S K Mani, A Diab, L Lefrancois, N Fares, P Merle, O Andrisani Oncogene.2017; 36(17): 2435. CrossRef
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Hepatoblastoma(HB) is a rare embryonic malignant tumor of the liver. Most morphological studies on HB have limited to the histological characteristics and only 3 cases of HB have been described in the cytology literature. We present 2 cases of HB occurring in children aged 1 year and 3 years, respectively. The distinctive cytologic features of fine needle aspiration of HB were clusters of tumor cells showing acinar and trabecular pattern, smaller tumor cells with a high nuclear-cytoplasmic ratio and hyperchromatic nuclei having prominent nucleoli, and the presence of extramedullary hematopoiesis and osteoid material. These features were also found in the cell block and the biopsy specimen, and appeared very useful in the differentiation of HB from hepatocellular carcinoma.
We report 4 cases of malignant thymoma which were composed of 2 cases of invasive thymoma and 2 cases of thymic carcinoma. The cytologic findings of invasive thymoma were similar to those of benign thymoma. The distinctive cytologic features of thymic carcinoma were necrotic background, irregular clusters and individually scattered arrangement of anaplastic epithelial cells, and some scattered mature small lymphocytes. These findings may be found in the Hodgkin'slymphoma, seminoma, and metastatic squamous cell carcinoma, undifferentiated carcinoma, and large cell carcinoma of the. lung. But, the feature of irregular clustering of anaplastic epithelial cell having scanty cytoplasm was different from Hodgkin'slymphoma and seminoma. Clinical and radiologic findings as well as cytologic finding were helpful in differential diagnosis of thymic carcinoma from metastatic carcinoma.
BACKGROUND High microsatellite instability (MSI-H) colorectal carcinomas (CRCs) with numerous mutations in the microsatellite sequence are characterized by a right-sided preponderance, frequent peritumoral and intratumoral lymphocytic infiltration, and frequent mucin production.
However, no study has correlated anatomic site and type of genetic changes with clinicopathologic changes. METHODS We analyzed the histopathologic features of 135 MSI-H CRCs and compared them to 140 microsatellite stable (MSS) CRCs. Histopathologic changes in MSI-H were further analyzed according to anatomic sites and genetic changes. RESULTS MSI-H CRCs showed previously reported clinicopathologic findings; a right-sided preponderance, an increased number of mucinous carcinomas, and peritumoral lymphoid reactions (p<0.001 for each variable). Increased serum CEA levels showed an MSS CRC preponderance (p=0.013).
We further analyzed the histologic differences between right- and left-sided MSI-H tumors. We found that MSI-H CRCs on both sides had similar clinicopathologic findings, except for higher tumor stage (p=0.048) and less frequent abnormal CEA levels in left-sided MSI-H tumors (p=0.027). We found that not all clinicopathologic features were different between hereditary nonpolyposis colorectal cancers (HNPCCs) and sporadic MSI-H CRCs. CONCLUSIONS These findings indicate that MSI-H CRCs of the left colon have similar clinicopathologic characteristics as right-sided MSI-H CRCs. We did not find any significant clinicopathological difference between HNPCCs and sporadic MSI-H CRCs.
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Fibroblast Growth Factor Receptor 1 Gene Copy Number and mRNA Expression in Primary Colorectal Cancer and Its Clinicopathologic Correlation Yoonjin Kwak, Soo Kyung Nam, An Na Seo, Duck-Woo Kim, Sung-Bum Kang, Woo Ho Kim, Hye Seung Lee Pathobiology.2015; 82(2): 76. CrossRef
Kupffer cells are tissue macrophages (histiocytes) fixed in hepatie sinusoids. Since malignant hepatocytes are the only tumor parencymal cells of the hepatocellular carcinoma, theoretically there are no Kupffer cells within the hepatocellular carcinoma. To clarify whether it is true or not, 12 cases of hepatocellular carcinoma of the trabecular type with some extents of the non-neoplastic surrounding liver were subjected to immunoperoxidase staining for lysozyme and S-100 protein and the results are as follows.
1) Kupffer cells were stained positively by the immunoperoxidase staining for lysozyme but not for S-100 protein, indicating that they are monocyte derived macrophages. 2) Kupffer cells were also present within the hepatocellular carcinoma, but were 2-7 times fewer within the hepatocellular carcinoma than in the non-neoplastic areas (p<0.05). 3) The non-neoplastic hepatic tissue of patients with serum HBsAg shows a tendency to have more kupffer cells than those without HBsAg.
BACKGROUND Hepatocellular cholestasis denotes the alteration of bile secretion by hepatocytes. The causes, degree of hepatocyte injury and concomitant bile duct loss are considered to influence the clinical course. METHODS The causes and pathological features of hepatocellular cholestasis were analyzed in 62 cases of liver biopsies; and the causes of primary biliary cirrhosis, primary sclerosing cholangitis, and biliary obstruction were not included. RESULTS The mean age of the patients was 42.2 years, and the ratio of male to female was 1.8:1. Fifty-eight cases (94%) showed cholestatic hepatitis, and 4 cases (6%) showed pure cholestasis without hepatitis activity. The majority of the cases (52 cases, 84%), including 19 cases of herbal medicine, was related to drugs. Loss of bile duct was found in 12 cases (19%), which were all cases of chronic cholestasis. All of them had drug histories, including 9 cases of herbal medicine. Clinical follow-up was performed in 9 out of the 12 cases with bile duct loss, and all of them showed elevated total bilirubin and/or alkaline phosphatase levels for more than 6 months. CONCLUSION Drugs are the major cause of hepatocellular cholestatic hepatitis/cholestasis; and information about drugs, including herbal medicines, should be considered for proper evaluation of liver biopsy with hepatocellular cholestasis. Bile duct loss should be evaluated in the cases of chronic hepatocellular cholestasis, especially in drug induced cases.
Young Nyun Park, Ho guen Kim, Chae Yoon Chon, Jae Bok Park, Jin Hee Sohn, Seung Ha Yang, Eun Sil Yu, Mi Seon Lee, Ja June Jang, Hee Kyung Chang, Jong Jae Jeong, Dae Young Kang, Yong Il Kim, Chan Il Park
The terms chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and chronic lobular hepatitis (CLH) should be discontinued in favor of etiologic terminology.
The activity of necro-inflammation and the degree of fibrosis should be evaluated for grading the severity and for the stage of disease. Members of the Korean Study Group for the Pathology of Digestive Diseases reviewed 30 cases of chronic hepatitis and reached the following consensus: 1) The pathology report of the biopsy samples with features of chronic hepatitis should include the etiology, grade and stage. 2) Grade and stage should be semiquantitatively evaluated as none, minimal, mild, moderate and severe. 3) For grading, lobular activity and periportal activity should be evaluated, separately. 4) To avoid confusion with other grading systems, simple report using descriptive terms rather than numerical records is recommended in daily practice.
Criteria for each grade and stage should be presented and discussed. Histologic grading and staging of chronic hepatitis by new standardized guidelines will give more information about the prognosis as well as the present status of hepatitis. The terms CAH, CPH and CLH may be used in parentheses to facilitate relearning.
To understand better the complex natural course of HBV infection, the expression patterns of HBcAg and HBsAg in the liver of 51 inactive serum HBsAg carriers (24 CPH and 27 NPD) were studied by immunohistochemical methods. The inactive serum HBsAg carriers were devided into 3 groups by the following expression patterns of serum HBeAg/anti-HBe status and tissue HBcAg and HBsAg. Pattern A (18 cases) : HBeAg+, cHBcAg+ (94.4%), mHBsAg+ (61.1%), pATTERN B (14 cases) : anti-HBe+, nHBcAg+, cHBsAg+, Pattern C (19 cases) : anti-HBe+, HBcAg-, cHBsAg+ (89.5%). There were no significant differences between CPH and NPD, lthough the core free pattern was more common in the latter. The cHBcAg was expressed in 17 of 18 (94.4%) HBeAg seropositive cases but only one of 33 cases with serum anti-HBe, suggesting that the cHBcAg is intimately related to HBeAg. Since the inactive HBsAg carriers also expressed cHBcAg and/or mHBsAg, the necro-inflammatory activity of HBV infected liver is assumed to depend on the host immune response rather than their presence alone
BACKGROUND Although it was suggested that constitutive extracellular signal regulated kinase (ERK) activation plays a pivotal role in intracellular signal transduction related to oncogenesis, a consistent relationship between constitutive ERK activation and oncogenesis has not yet been clearly demonstrated. The purpose of this study is to evaluate the expression frequencies and pattern of phosphorylated ERK (p-ERK) in the non-small cell lung carcinoma (NSCLC) and to evaluate whether p-ERK is a useful prognostic factor. METHODS One hundred sixty cases of NSCLC tissue specimens were investigated by immunohistochemical staining for p-ERK.
Clinicopathologic values (tumor stage, cell type, differentiation and presence of metastasis) and p-ERK expression of normal alveolar pneumocytes around NSCLC were compared with the incidence of tumor p-ERK expression. RESULTS Fifty-three out of 160 cases (33%) of NSCLC showed expression of p-ERK. There was no statistical correlation between the expression of p-ERK in the NSCLC neoplastic cells and the corresponding tumor stage, cell type and presence of metastasis. There was statistical significance between the expressions of p-ERK in alveolar pneumocytes around NSCLC (odds ratio: 6.130). CONCLUSIONS Based on these results, we suggest that p-ERK expression is not useful in predicting the prognosis of NSCLC. In regard to the theory of "field cancerization" and the phenomenon of "allele-specific loss or allele-specific mutations", the statistically significant p-ERK expression in alveolar pneumocytes around NSCLC suggests that constitutive ERK activation is involved in the early stage of NSCLC carcinogenesis rather than in proliferation, differentiation or metastasis of NSCLC.
In order to clarify the preneoplastic nature of large regenerative nodules without dysplastic change, we analysed the clonality of hepatocellular carcinomas (HCCs) and large nodules, diameter > or =0.5 cm, of cirrhotic liver by X-linked human androgen receptor (HUMARA) gene assay, using the principle of random X chromosome methylation and inactivation in female. Ten cases of HCC and 5 cases of large nodules without dysplasia from 9 female patients were selected. All the tumors, large nodules and paired normal control cells were selectively microdissected from deparaffinized hematoxylin and eosin stained slides. Genomic DNA was isolated and digested with HhaI. Polymerase chain reaction(PCR) amplication of the HUMARA locus was performed using 32P-a-dCTP containing PCR mixtures. The PCR amplified products were separated by gel electrophoresis and analysed by autoradiography. Nine HCCs from 8 patients were monoclonal and 1 case was polyclonal and the remaining 1 case was not polymorphic at the HUMARA locus. The HCC case which showed polyclonality contained many inflammatory cells. All the large nodules were polyclonal by HUMARA assay. These results suggest that all or most of the cells composing the large regenerative nodules without dysplasia are polyclonal. This assay may be informative for the differentiation between regenerative and preneoplastic nodules in cirrhotic liver and the size of nodule may be not important in hepatocarcinogenesis.
Chemically induced epiderml carcinogenesis is usually divided into two stages, the initiation and promotion. The initiation involves conversion of some epidermal cells into latent neoplastic cells and the promotion is proliferation of the transformed cells. As immunosurveillence is thought to be a host defense against tumors, Langerhans cells, being essential in initiation of local cutaneous immunologic reaction, is suggested to be important in the carcingenesis of the epidermis. This study is attempted to investigate the epidermal proliferative changes in mice induced by application of 12-0-tetradecanoy1-phorbol-13-acetate(TPA) on the skin initiated with 7, 12-dimethylbenzanthracene(DMBA) and its relationship with Langerhans cell. Ninty five male inbred BALB/c mice weighing 20~25 g were divided into five groups; the 33 week-group, the 21 week-group, the 12 week-group and the 4 week-group according to the duration of carcinogen application, and the control group. The carcingen was applied with a brush on the dorsal skin of mice after depilation. Ten days after application of 800 nmole DMBA in 0.4 cc acetone, 20 nmole TPA in 0.4 cc acetone was applied twice per week and the control group was applied with the same amount of acetone for 4 weeks. Animals were sacrificed 3 days after the last application of TPA. One hour before sacrifice, bromodeoxyuridine(BrdU) (1 mg/g) was injected via the tail artert for BrdU stain of S phase cells. A strip of dorsal skin was used for hematoxylineosin stain, immunohistochemical stain for BrdU and la antigen of Langerhans cell, and flow cytometry. The results are as follows: 1. Cellular proliferation, hyperkeratosis and dysplasia of the epidermis were increased in relation to duration of carcingen application. Papillomas were developed 12 weeks after application of the carcingen. 2. BrdU labelling and proliferative indices of the 20 weeks' application group were significantly higher than those of the 12 weeks' application group. The number of Langerhans cell was decreased markedly ater 4 week' application of the carcinogen. 3. All epiedrmal lesions including a case of squamous cell carcinoma were diploidy in flow cytometry. It is thought that disturbance of immunosurveillence, caused by depletion of Langerhans cell, may permit proliferation of epidermal cells. Although abnormal quantitative change of nuclear DNA has not occurred even when the epidermal proliferative activity and dysplastic change were increased markedly, it is thought that the occurrence of structural change of chromosome is remained to be clarified.
Forty-nine lobectomized hepatocellular carcinomas(HCC) were classified according to the gross anatomical features.
Because the presence of cirrhosis in the remaining liver has a good clinico-pathological implication, cases of HCC were divided into non-cirrhotic(non-LC) and cirrhotic(LC) groups.
In both groups, the tumors themselves belonged to either expanding, focal spreading, spreading or mixed type. Another special type, which has been called a "diffuse type" is added in the LC group with the name of "cirrhotomimetic type" Among 49 cases, 21 belonged to the non-LC group and 28 to the LC group. Most common was expanding type(20 cases, 40.8%), which was followed by spreading(32.7%), focal spreading(16.3%), mixed(6.1%) and cirrhotomimetic(4.1%) types. Expanding type of the LC group was the single most common type(13 cases, 26.5%). The accordance rate of gross typing was 0.94. Tumor masses of the LC group showed a greater tendency of having a fibrous capsule(60.7%) and a lobulated cut surface(82.1%), in contrast to those of the non-LC group (28.6% and 42.9% respectively). The patient's age and the HBsAg seropositivity were not different between the groups and between the types. Increased serum level of AFP was particularly frequent in the spreading type(81.3%) of both groups and in the cirrhotomimetic type(100%).
Although methotrexate(MTX) has been known to have many side effects, especially toxicity on the hemopoietic cells and the liver, it has been used as a potent anticancer drug and for the treatment of psoriasis or rheumatoid arthritis. The severity of hepatotoxicity varies from mild fatty change to chronic active hepatitis(CAH) and cirrhosis. We experienced two cases of MTXinduced CAH in patients with psoriasis, which prompted us to report in view of the absence of biopsy proven MTX hepatotoxicity in the Korean literature.
Microscopically, the liver showed a distorted lobular architecture with portal fibrous expansion, piecemeal necrosis and bridging necrosis/fibrosis. The hepatic lobules revealed fatty changes of hepatocyte, focal hepatocytolysis, delicate collagen deposits along the space of Disse and the characteristically marked polyploid nuclear change of hepatocytes.
It is well known that histologic grade and tumor stage are important prognostic factors, and that the monoclonal antibody to proliferating cell nuclear antigen(PCNA) can recognize S-phase cells. The PCNA index of 53 transitional cell carcinomas(TCCs) of the urinary bladder was studied to evaluate its prognostic validity. The PCNA indices of TCCs ranged from 38 to 92, whih were quite different from that of normal transitional epithelium(9.4). The PCNA indices were significantly higher in tumors of the higher histologic grade and/or tumor stage(correlation coefficient 0.64 and 0.43; P=0.00). The PCNA index was particularly valuable in discriminating the superficial TCCs from the deeply invasive TCCs(67.1+/-15.46 and 79.9+/-9.70; P=0.000). Among TCCs of the same tumor stage, the histologic grade affected the PCNA index. However, TCCs of the same histologic grade revealed similar PCNA indices regardless of tumor stage. These results indicate that the PCNA index is an objective and reliable prognostic factor in TCCs, which is superior to the conventional histologic grade.
BACKGROUND Matrix metalloproteinase (MMP)-2 and MMP-9 degrade type IV collagen and are antagonized by the tissue inhibitors of metalloproteinase (TIMP)-2 and TIMP-1, respectively. METHODS We studied by immunohistochemistry the expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 in 72 cases of adenocarcinoma of the gallbladder. RESULTS The MMP-2, MMP-9 and TIMP-1 expressions were significantly higher in well/moderately differentiated adenocarcinomas than in poorly differentiated adenocarcinomas, in adenocarcinomas that had invaded the lamina propria/proper muscle than in those that had invaded the perimuscular connective tissue or beyond the serosa, and in adenocarcinomas with fungating growth than in those with infiltrative growth. The TIMP-2 expression showed a similar pattern without statistical significance. Regarding the status of lymph node metastasis, the MMP-2 expression was significantly higher in cases without lymph node metastasis.
The MMP-2 and MMP-9 expressions were significantly related to those of TIMP-2 and TIMP-1, respectively, with regard to depth of invasion, differentiation, and growth patterns of the adenocarcinomas. CONCLUSIONS MMP-2, MMP-9, TIMP-1 and TIMP-2 are suggested to play important roles in the progression to early invasion of adenocarcinomas, in which the function of MMP-2 is inhibited by TIMP-2.
Adreno-hepatic fusion is rare condition defined as adhesion of the liver and right adrenal cortex with close intermingling of the respective parenchyme. It is suggested to be an aging phenomenon, because its incidence is much higher in older age group. Clinically it may pose a problem of operability of the organ involved. We report a case of incidentally found adreno-hepatic fusion in a 49 year old female patient with adenocarcinoma of the sigmoid colon. The segementectomy of VIII segement of the liver was done due to a 6 4 cm sized metastatic nodule of adenocarcioma.
Pathological examination of the liver revealed an ovoid shaped, 1 0.5 cm sized adrenal cortical tissue. It was subcapsularly located and about 1cm apart from the metastatic adenocarcinoma with an intervening normal hepatic tissue. The adrenal tissue was mainly composed of zona fasciculata without medullary tissue. In the interphase, the adrenal tissue and liver tissue were admixed closely and partially septated by thin fibrous tissue. There was no inflammatory response to the heterotropically located adrenal tissue and there was no symptom related to the adrenal gland.
p21 is a universal inhibitor of cyclin-dependent kinase (cdk) and of cell-cycle progression.
p21 expression is variable according to the type of tissue and the pathologic condition. To study the role of p21 in the multistep hepatocarcinogenesis, the expression of p21, p53 and Ki-67 was investigated in 53 cases of inactive liver cirrhosis, 4 cases of low grade dysplastic nodules, 3 cases of high grade dysplastic nodules, 7 cases of early hepatocellular carcinomas (HCCs), 27 cases of small HCCs (< or =3 cm), and 52 cases of advanced HCCs (>3 cm). p21 expression was not detected in liver cirrhosis, low grade dysplastic nodules, high grade dysplastic nodules and early HCCs which were mitotically inactive. p21 expression was significantly increased in small HCCs and advanced HCCs which were mitotically active. p21 expression was significantly correlated with Ki-67 labelling indices. p53 protein was not expressed in liver cirrhosis, dysplastic nodules, and early HCCs. The expression of p53 protein was, however, significantly increased in small and advanced HCCs. The p21 expression was not correlated with p53 expression. Therefore, p21 is suggested to play a role in the mitotically active small and advanced HCCs, but not in the mitotically inactive lesion of dysplastic nodules and early HCC in multistep hepatocarcinogenesis.
These findings suggest that homeostatic mechanism of growth control is not totally destroyed in HCC.
Hepatic veno-occlusive disease (VOD) is a rare disease due to occlusion of the terminal hepatic venules and/or sublobular veins, which is a result of endothelial damage from pyrrolizidine alkaloids in herbal teas, irradiation of the liver, or chemotherapy particularly in association with bone marrow transplantation. We recently experienced three cases of VOD developed after radiation therapy. Two cases occurred in hepatocellular carcinoma patients of a 37-year-old man with B viral chronic hepatitis and a 22-year-old man with B viral cirrhosis and the other in a 64-year-old patient with esophageal squamous cell carcinoma.
For the treatment of hepatocellular carcinoma, chemoembolization with lipiodol and adriamycin, and external irradiation on the liver mass were done. The total radiation dose was 5400 cGy and 3000 cGy in each case. Five months and 3 months after irradiation, respectively, the resected liver masses showed extensive necrosis due to pre-operative treatment. To treat esophageal carcinoma, pre-operative concurrent chemotherapy of 5-FU and radiation of 4500 cGY were done.
One month after irradiation, the radical esophgectomy and wedge biopsy of the liver were done. The liver of all 3 cases showed a dark red appearance with severe congestion in contrast to the pale brown normal liver, which was not included in the radiation field. On micoscopic examination, the terminal hepatic venules and sublobular veins showed subintimal edema, fibrin deposition, and partial or total luminal occlusion by loose fibrous tissue. The centrizonal sinusoids were markedly dilatated and congested with atrophy of hepatocytes.
We report a case of non-cirrhotic portal hypertension in a 73 year-old woman, who had 19-year history of idiopathic myelofibrosis. There were esophageal varix, splenomegaly, and ascites. The biopsied liver showed irregular sinusoidal/ perisinusoidal fibrosis and occasional central-to-central fibrous connection. In areas with extensive fibrosis, coarse collagen fibers filled the sinusoidal spaces and compressed hepatocytes. However, nodular regeneration was absent.
Double immunohistochemical stain for smooth muscle actin and proliferation cell nuclear antigen (PCNA) revealed diffusely activated stellate cells, some of which showed nuclear PCNA staining.
There was also extramedullary hematopoiesis with bizarre megakaryocytes. The portal vein and its branches were patent. Idiopathic myelofibrosis is a rare cause of non-cirrhotic portal hypertension: the portal hypertension was considered to be the result of sinusoidal/perisinusoidal fibrosis in this case.
This study was undertaken to elucidate the short-term effect of iron on the hyperplastic lesions of experimental hepatocarcinogenesis. The Solt-Farber's resistant hepatocyte model was chosen for the experiment, and Sprague-Dawley rats wee divided into six groups: normal control, iron-rich diet administration with or without hydroxyquinoline. The iron content, microscopic changes, bromodeoxyuridine(BrdU) labelling index and the DNA polidy were studied. In the carcinogen administered group, oval cell proliferation and consecutive hyperplastic lesions of hepatocyte developed regardless of iron administration. The hepatic iron content was increased rimarkably by iron administration, but gradually decreased as the hyperplastic lesions developed in carcinogen administered groups. Although the administration of iron without carcinogen induced hepatic accumulation of stainable iron, the hyperplastic lesions appeared to be lack of it. BrdU labelling indices of the oval cells and the hyperplastic lesions of hepatocyte were very high and were not significantly altered by iron administration. Most liver cells had diploid or tetraploid DNA content, but there was an increase of diploidy as the development of hyperplastic lesions regardless of iron administration. The results indicate that the chemical carcinogen-induced hyperplastic lesions of hepatocyte do not accumulate iron, and that short-term iron administration does not affect the development of hyperplastic lesions and their proliferative activity and DNA ploidy.
Sclerosing hepatic carcinoma (SHC) is composed of slender cords or small nests of tumor cells with peripheral palisading, and abundant intervening sclerosis. The tumor seems to have the histologic features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma. To evaluate the phenotypic expression of SHC and to investigate its cellular origin, immunohistochemical studies on three cases of SHC were performed. In all cases, the tumor cells showed positive staining for cytokeratins AE1, AE3 and 19, carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). The expressions of cytokeratins AE1 and 19 were stronger in the palisading cells than the interior of the cords and nests. Conversely, CEA and EMA were expressed mainly in the inner portion. Alpha-fetoprotein was expressed in only one case, mainly in the palisading cells. In summary, SHC has the histological as well as the immunohistochemical profiles intermediate between HCC and cholangiocarcinoma, and the immunohistochemical profile suggests that SHC arises from primitive hepatoblast with a tendency of differentiation to the bile duct epithelium.
The number of Kupffer cells was evaluated in hepatocellular carcinomas, including 18 primary lesions, 3 tumor emboli within the portal vein radicles and 4 metastatic lesions and in non-neoplastic liver adjacent to the primary lesions, to persue the origin of Kupffer cells dwelling in hepatocellular carcinoma. Hepatocellular carcinomas of the sinusoidal(trabecular) type were carefully selected, and excluded were those carcinomas which showed inflammation or other changes evoking inflammation. The immunohistochemical stains for CD 68 and lysozyme were done to identify Kupffer cells and to draw the mean Kupffer cell number per high power microscopic field of each lesion. Kupffer cell was most numerous in primary lesions followed by tumor emboli and still fewer in metastatic lesions. The Kupffer cell number in the primary lesions of hepatocellular carcinoma was in turn smaller than that of the adjacent non-neoplastic liver. The results suggest that, during the early neoplastic transformation, sinusoids of the non-neoplastic liver could creep into the carcinomatous tissue accompanying Kupffer cells.
Jin Hee Sohn, Kyung Me Kim, Seoung Wan Chae, Woo Ho Kim, Woo Sung Moon, Young Nyun Park, Chul Gun Park, Eun sil Yu, Hee Kyung Jang, Hee Jin Jang, Jong Jae Jung, Jin Sook Jung, So Young Jin, Jong Sang Choi, Dae Young Kang
BACKGROUND Mucin producing cystic neoplasms, such as mucinous cystic tumor (MCT) and intraductal papillary mucinous tumor (IPMT) of the pancreas, are uncommon but become increasing in their incidences. The pathologic classification and biologic potential of these neoplasmsremain the subject of controversy. METHODS The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists analyzed the clinicopathologic characteristics of 85 casesof MCT and 72 cases of IPMT and examined the expression patterns of p53, CEA and MUC1. RESULTS IPMT was located largely in the head, and showed connection with the main pancreatic duct (MPD, 68.1%), no ovarian-like stroma (0/72), and presence of intervening intratumoralnormal or atrophic parenchyma. On the other hand, MCT was located largely in thetail (73%), and showed common ovarian-like stroma (66/80), rare connection with the MPD(7/85) and no intervening pancreatic parenchyma. CEA and p53 immunoexpressions weresignificantly increased from adenoma through borderline to carcinoma, but MUC 1 was expressedonly in the invasive carcinoma among cases of MCT and IPMT. CONCLUSIONS The tumorlocation, ovarian-like stroma, connection with the MPD and intratumoral intervening nonneoplastictissue were helpful in the differential diagnosis between IPMT and MCT. CEA and p53expressions can be indicators of malignancy, while MUC 1 expression can indicate invasion.
To elucidate the effect of copper on the 3'-methyl-4-dimethylaminoazobenzene(3'-MeDAB) induced hepatic carcinogenesis, Sprague-Dawley rats were divided into 4 groups according to 3'-MeDAB and copper administration: I. noraml control, II. copper only, III.
3'-MeDAB only, IV. 3'-MeDAB plus copper. The animals of groups III and IV were fed experimental diet containing 0.06% 3'-MeDAB. Copper was administrated intraperitoneally in a dose of 0.5 mg, twice a weak. Animals were sacrificed at different intervals. Liver weight, hepatic copper content and gross and microscopical changes of the liver were examined and the cell kinetics of various lesions in the hepatic carcinogenesis was studied by applying the immunohistochemical method for bromodeoxyuridine(BrdU). The hepatic copper content was significantly increased in animals given copper but returned to the normal value after cessation of adminstration. 3'-MeDAB administration caused oval cell proliferation and produced hyperplastic nodules, cholangiofibrosis and carcinoma of the liver. Simultaneous administration of copper did not alter the incidence of 3'-MeDAB induced lesions, except for carcinoma. The liver weight and the size of hepatic nodules and masses were smaller in group IV than in group III. The liver weight as well as the nodularity and the mass formation continued to increase affect cessation of 3'-MeDAB administration. Copper did not affect the BrdU labelling indices of the hepatic lesions induced by 3'-MeDAB. The oval cell proliferation and the BrdU labelling indices of the oval cell and the hyperplastic nodule were decreased, but the incidence of cholangiofibrosis and its BrdU labelling index were still elevated after cessation of 3'MeDAB administration. These findings indicate that copper could delay the developement of 3'-MeDAB induced hepatic lesions, but not suppress, since copper does not stay long enough to accumulate in the rat liver, and that copper could not affect the proliferation of 3'-MeDAB induced hepatic lesions once developed.
Hepatic changes in eight cases of systemic lupus erythematosus(SLE), were studied to evaluate the nature of hepatic injury of SLE and its relation to lupoid hepatitis.
Common histologic changes of the liver in SLE included intralobular necro-inflammatory activities, fatty change, canalicular bile stasis and mild perivenular and Disse space fibrosis. The fatty change and intralobular fibrosis were thought not to be due to SLE itself but associated with steroid administration or chronic alcoholic consumption. The necro-inflammatory changes were usually mild and features of chronic active hepatitis with periportal destruction occured in one case. Symptoms related to the involvement of many other organs than the liver appeared much frequently in patients with SLE than lupoid hepatitis, suggesting that the SLE involving liver and the lupoid hepatitis are different diseases.
Atypical laryngeal carcinoid is a rare tumor with a poor prognosis, mostly occurring in the supraglottic larynx. It is a subtype of neuroendocrine carcinoma which should be separated from typical carcinoid and small cell carcinoma.
The histogenesis and standardized classification of laryngeal neuroendocrine carcinoma have not been clearly defined. In this report, we present two cases of atypical laryngeal carcinoid, one occurring in a 67 year old male and the other in a 54 year old female. Indirect laryngoscopy revealed a polypoid supraglottic mass, approximately 3 cm in diameter. Microscopically, each case showed a moderate degree of pleomorphism, tumor necrosis and frequent mitoses.
The immunohistochemistry revealed a strong positive reaction for chromogranin, neuron specific enolase and cytokeratin.
Each patient had distant metastasis, noted within 4 months after resection (liver and stomach), and died postoperatively at 5 and 20 months, respectively. A brief review of the literature concerning the biological behavior, histogenesis and pathology of atypical laryngeal carcinoid was performed.
Biliary cystadenoma of the liver is a rare multilocular cystic neoplasm of biliary origin. it occurs most often in middle aged women and rarely in children. Histogenesis of this tumor is uncertain. It may be developmental in origin arising from aberrant hamartomatous bile ducts or ectopic rests of embryonic biliary cystadenoma of the liver discovered at 8 month of intrauterine fetal life. This case supports its congenital theory.
Cases sharing features of both primary biliary cirrhosis and autoimmune hepatitis have been reported as a mixed type, overlap syndrome, immunocholangitis and autoimmune cholangiopathy. A primary biliary cirrhosis- autoimmune hepatitis overlap syndrome is unusual and characterized by overlapping features; cholestasis, high titer of alkaline phosphatase, bile duct damage and granulomas in the liver biopsy, high antinuclear antibody, increased IgG and IgM and intra-acinar hepatitis with piecemeal necrosis. Autoimmune mechanisms are thought to play a major role in the pathogenesis of the overlapping syndrome and the bases of immunosuppressive therapy. A 58-year-old female patient shows overlapping clinical and laboratory findings, chronic active hepatitis in initial liver biopsy which transits to primary biliary cirrhosis with cholangitis and granulomas.
This is a case of hepatobiliary lesion showing overlapping features of both primary biliary cirrhosis and autoimmune hepatitis over 3-year period.
This report presents a case of an atypical nodule arising in a hepatocellular adenoma(HCA) in a non-cirrhotic liver of a 42-year-old man. The patient had been relatively healthy until he developed right upper abdominal pain. Abdominal sonography and computerized tomogram revealed a 7.5x7cm sized mass in the right inferior segment of liver. The mass revealed the histologic features of HCA. At near center of the HCA, was found a I cm sized discrete nodule, a nodule within a nodule. The nodule revealed higher cellularity than the HCA and was composed of monotonous hepatocytes with an increased nuclear-cytoplasmic ratio, resembling atypical adenomatous hyperplasia. Interestingly, the atypical nodule showed a focal pseudoacinar arrangement of tumor cells. The histologic features of the atypical nodule arising in HCA may the morphological sequence of transformation from HCA to hepatocellular carcinoma
Alagille syndrome is a rare autosomal dominant disorder showing complicated systemic manifestations, although the hepatic manifestations are predominant in many patients. We report a case of Alagille syndrome in a male baby who presented with a heart murmur at 2 days old and his echocardiography showed aortic stenosis. He presented with acholic stool and jaundice at 3 months old and a liver biopsy revealed paucity of the interlobular bile duct in the portal tract. This progressed to cirrhosis, for which a liver transplantation was performed at 10 months old. The explanted liver showed biliary-type cirrhosis with severe cholestasis. There was an absence of the interlobular bile ducts on microscopic examination. Bile duct paucity, associated with cholestasis, a peculiar face (prominent forehead, deep-set eyes, pointed mandible and bulbous nasal tip), and cardiac anomaly were observed, which were consistent with Alagille syndrome. He died of heart failure.