bromochloroacetic-acid and Gallbladder-Neoplasms

A 75-year-old man presented to his physician with weakness, anorexia, and constant right upper quadrant pain. He underwent a laparoscopic cholecystectomy, which was converted to an open cholecystectomy due to presumed adhesions. Direct examination of the liver was negative for masses or lesions. A CT scan was negative for masses or nodules. The gallbladder was 8.5 x 2.5 cm(2), with a diffusely thick wall measuring 2.5 cm. Microscopic examination showed a monomorphic tumor consisting of cells with increased nuclear:cytoplasmic ratio and occasional nucleoli, infiltrating the entire gallbladder uniformly. The tumor cells that reacted to antibodies directed against HepPar1, CAM 5.2, CK19 and scattered cells were immunoreactive for CD117, CD34, and CD56. This immunohistochemical profile suggested a 'hepatocellular progenitor cell tumor of the gall bladder'. This report is, to our knowledge, the first such case of a tumor of this cell type reported in the gallbladder. In addition, we present a review of the literature.

Topics: Aged; Antibodies, Monoclonal; Antigens, CD34; Biomarkers; CD56 Antigen; Gallbladder Neoplasms; Hepatocytes; Humans; Immunohistochemistry; Keratins; Male; Proto-Oncogene Proteins c-kit

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7-, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20-, MUC2-). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.

Topics: Adenocarcinoma; Adenoma; Ampulla of Vater; Common Bile Duct Neoplasms; Gallbladder Neoplasms; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Mucin 5AC; Mucin-2; Mucins; Prognosis

The objective of this study was to define the sensitivity and clinical implications of the immunohistochemical detection of lymph node micrometastases in patients with gallbladder carcinoma (GBC).. The authors examined a total of 385 regional lymph nodes taken from 26 consecutive patients with GBC who had undergone a radical resection. Histologic sections of the primary tumor and regional lymph nodes in each case were stained with both hematoxylin and eosin and an antibody against cytokeratins 8 and 18 (CAM5.2). A "micrometastasis" was defined as a metastasis missed on routine histologic examination with hematoxylin and eosin but detected by immunohistochemical examination with CAM5.2. Survival rates were calculated only in patients with Stage II or more advanced stage disease.. All primary tumors were positive for CAM5.2. Routine histologic examination revealed 53 positive lymph nodes that were stained consistently with CAM5.2. Another seven lymph nodes had micrometastases. Patients with micrometastases showed a significantly worse survival rate than those without micrometastases (P = 0.037, log rank test). Among patients with no lymph node disease on routine histologic examination, there was a trend toward a worse survival rate in those with lymph node micrometastases (P = 0.10, log rank test). The paraaortic lymph nodes were involved more frequently in patients with lymph node micrometastases than those without (P = 0.009, Fisher exact test).. The immunohistochemical detection of lymph node micrometastases using CAM5.2 is feasible in GBC patients and is useful in predicting survival in patients undergoing radical resection. Lymph node micrometastases may be an indicator of widespread lymph node disease in patients with GBC.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Sensitivity and Specificity; Survival Rate

Topics: Biomarkers, Tumor; Endometrial Neoplasms; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Middle Aged; Pain; Positron-Emission Tomography; Radiography, Abdominal; Receptors, Estrogen; Receptors, Progesterone; Tomography, X-Ray Computed; Ultrasonography; Vimentin

Tumor invasion of the peritoneal membrane may have an adverse prognostic significance, but its histopathologic features can be diagnostically difficult to recognize. We observed that local peritoneal injury associated with tumor invasion is characterized by activation and proliferation of serosal stromal cells that express cytokeratin, a characteristic property of injured serosal membranes that may have diagnostic utility. To explore this, we examined 120 primary tumors of the gastrointestinal tract and pancreaticobiliary system using cytokeratin and elastic stains to assess for tumor invasion of peritoneal membranes. Peritoneal invasion by tumor was associated with retraction, splaying, and destruction of the elastic lamina and proliferation of keratin-expressing stromal cells of serosal membranes. All 82 peritoneal invasive tumors were characterized by neoplastic cells that invaded the elastic lamina and the serosal connective tissue with neoplastic cells that abutted or were surrounded by keratin-positive stromal cells, whereas all 38 tumors limited to the subserosa showed none of these features. The diagnosis of tumor invasion of peritoneal membranes is enhanced by the combined use of cytokeratin and elastic stains, which in turn would enable better histopathologic correlation with patient treatment and outcome.

Topics: Gallbladder Neoplasms; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Keratins; Pancreatic Neoplasms; Peritoneal Neoplasms; Peritoneum

The presence of para-aortic lymph node metastasis in biliary cancer negatively impacts prognosis. The present study aims to immunohistochemically identify and evaluate the clinical significance of para-aortic lymph node micrometastases in 66 patients who had undergone curative resection of biliary cancer.. We used an antibody against cytokeratins 7 and 8 (CAM5.2) to immunostain 529 para-aortic lymph nodes that were negative according to conventional analysis from 66 patients with biliary cancer.. We detected CAM5.2-positive occult carcinoma cells in para-aortic lymph nodes from 3 (5%) of the 66 patients and in 3 (0.6%) of the 529 para-aortic lymph nodes. One of the 3 patients also had micrometastasis in the regional lymph nodes. All 3 patients with para-aortic lymph node micrometastasis are alive at 45, 48 and 90 months after surgery despite having locally advanced cancer.. Occult cancer cells were identified in para-aortic lymph nodes from 5% of patients with node-negative biliary cancer, yet these patients have survived over the long term. The presence of para-aortic nodal micrometastasis might not have an influence on survival. However, further studies using a greater number of patients are required to support this notion.

Topics: Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers; Carcinoma; Cholangiocarcinoma; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Retrospective Studies

To investigate whether immunohistochemically demonstrated lymph node micrometastasis has a survival impact in patients with advanced gallbladder carcinoma (pT2-4 tumors).. The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, few reports have addressed this issue with regard to gallbladder carcinoma.. A total of 1476 lymph nodes from 67 patients with gallbladder carcinoma (pN0, n = 40; pN1, n = 27) who underwent curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were correlated with clinical and pathologic features and with patient survival.. Lymph node micrometastases were detected immunohistochemically in 23 (34.3%) of the 67 patients and in 37 (2.5%) of the 1476 nodes examined. Of the 37 nodal micrometastases, 21 (56.8%) were single-cell events, and the remaining 16 were clusters. Five micrometastases were detected in the paraaortic nodes. Clinicopathologic features showed no significant associations with the presence of lymph node micrometastases. Survival was worse in the 27 patients with pN1 disease than in the 40 with pN0 disease (5-year survival; 22.2% vs. 52.6%, P = 0.0038). Similarly, survival was worse in the 23 patients with micrometastasis than in the 44 without micrometastasis (5-year survival; 17.4% vs. 52.7%, P = 0.0027). Twenty-eight patients without any lymph node involvement had the best prognosis, whereas survival for the 11 patients with both types of metastasis was dismal. The grade of micrometastasis (single-cell or cluster) had no effect on survival. The Cox proportional hazard model identified perineural invasion, lymph node micrometastasis, and microscopic venous invasion as significant independent prognostic factors.. Lymph node micrometastasis has a significant survival impact in patients with pN0 or pN1 gallbladder carcinoma who underwent macroscopically curative resection. Extensive lymph node sectioning with keratin immunostaining is recommended for accurate prognostic evaluation for patients with gallbladder carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Survival Analysis; Survival Rate

Macropathologic types of gallbladder cancer are mostly polyp type, intumescent type, and cauliflower form lump. Its histological types include well or poorly differentiated adenocarcinoma, mucinous adenocarcinoma, and undifferentiated cancer. This research was to explore the clinicopathologic features of gallbladder adenocarcinoma with marked stromal fibrosis.. Pathology of 19 cases of gallbladder adenocarcinoma with marked stromal fibrosis was observed using a light microscopy and SP immunohistochemistry. Clinicopathologic features of 19 patients were analyzed.. Most of the patients had long-term history of cholecystitis gallbladder calculus. B ultrasound showed that the gallbladder wall was irregularly thickened or presented nodosity. Observed with naked eyes, gallbladder adenocarcinoma with marked stromal fibrosis did not form cancer nodule and extrude into the gallbladder lumen, the gallbladder wall showed regional thickening, a few cases showed diffuse irregular thickening. Observed under a light microscope, the adenocarcinoma cells were mostly arranged as single layers, seldom arranged as multiple layers, and formed adenoid structures with different sizes, various shapes, and irregular arrangement; the nuclei were heterogenic with haryomitosis presented in a few cases; inflammatory cells were infiltrated in hyperplastic fibrous connective tissue of some cases. According to immune phenotyping, CK (AE1/AE3), CK (AE1), CK7 (OV-TL12/30), CK8 (C51), CK18 (Dc-10), CK19 (RCK108), and EMA (Mc-5) showed strong expression, CEA (COL-1), CK20 (Ks20. 4), and MUC-5AC (CLH2) showed moderate expression, and MUC-2 (B306. 1) showed weak expression; CK17 (E3) showed focal expression.. The clinical manifestation, macropathologic type, histological characteristics of gallbladder adenocarcinoma with stromal fibrosis are different from other types of adenocarcinoma. Its genesis may be related to chronic cholecystitis: long-term inflammation causes regional hyperplasia and heterogeneity of the gland body, lead to focal or regional thickening of the gallbladder wall, and result in gallbladder adenocarcinoma with stromal fibrosis finally.

Topics: Adenocarcinoma; Adult; Aged; Cholecystectomy; Diagnosis, Differential; Female; Fibrosis; Follow-Up Studies; Gallbladder; Gallbladder Neoplasms; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Male; Middle Aged

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cholecystectomy; Endosonography; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Liver; Lymph Node Excision; Neprilysin; Treatment Outcome

In order to evaluate the significance of altered expression of mucin and cytokeratin during gallbladder carcinogenesis, we characterized the expressional profiles of MUC1, MUC2, MUC5AC, MUC6, CK7 and CK20 in 33 normal mucosa, 31 adenomas, 55 dysplasias and 131 carcinomas of the gallbladder. In normal gallbladder mucosa, the expressions of MUC5AC and MUC6 were diffuse and MUC1 expression was absent. However, in adenomas, dysplasias and carcinomas, the expressions of MUC5AC and MUC6 tended to decrease, whereas MUC1 expression was elevated. MUC2 and CK20 were infrequently expressed in all of the gallbladder epithelia, but adenomas expressing MUC2 and/or CK20 were more frequently associated with carcinomas and showed a higher grade of atypia than those without these antigens. In carcinomas, MUC1 expression was related to invasive growth, lymph node metastasis and a non-papillotubular type, whereas MUC6 expression was related to non-invasive growth. CK7 was diffusely expressed in almost all lesions, but carcinomas with a loss of CK7 expression showed poor survival. In conclusion, normal gallbladder mucosa has a gastric phenotype, but during carcinogenesis and tumor progression, the gastric phenotype is gradually lost and the aberrant expression of MUC1 occurs. The intestinal phenotype is not common in the gallbladder.

Topics: Adenoma; Biomarkers, Tumor; Carcinoma; Cell Count; Gallbladder Neoplasms; Hospitals, University; Humans; Immunoenzyme Techniques; Keratins; Mucins; Phenotype; Survival Rate

Expression of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) helps to establish the origin of biliary and metastatic carcinomas. We investigated the expression of CK7 and CK20 in inflammatory, metaplastic and neoplastic conditions of the bile ducts, and evaluated possible relationships between the CK expression pattern and extrahepatic bile duct/gallbladder carcinomas (EBDCs) or intrahepatic bile duct carcinomas (IBDCs). We used immunohistochemistry for the investigation of 48 formalin-fixed, paraffin-embedded specimens grouped as: A) lithiasic or inflamed surgically resected extrahepatic bile ducts/gallbladders: all were CK7+/CK20+; B) percutaneous liver biopsies from patients with chronic hepatitis C primary biliary cirrhosis and primary sclerosing cholangitis: all were CK7+/CK20-; C) EBDCs: all were CK7+/CK20+, except for two cases which were CK7-/CK20-; D) IBDCs: all were CK7+/CK20-, except for one case showing CK20 positivity. Metaplastic changes were seen only among specimens in groups A and C: in these cases, CK20 was either focally or diffusely expressed. Our study suggests that the expression of cytokeratins under specific stimuli can be different from normal tissues, and that sometimes CK20 expression can be related to and precede the occurrence of metaplastic alterations.

Topics: Bile Duct Diseases; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Bile Ducts, Intrahepatic; Carcinoma; Cell Transformation, Neoplastic; Gallbladder Diseases; Gallbladder Neoplasms; Gene Expression Profiling; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins

Extraskeletal osteosarcoma is a rare malignant soft tissue tumor. Authors present the history of a 61-year-old woman who had bone like tissue in her gallbladder at cholecystectomy. Histology proved, it was extraskeletal osteosarcoma of the gallbladder. Such disease has not been previously reported in the literature. She developed metastatic disease five months after the operation: multiplex cystic-calcified metastases appeared in the abdominal wall and in the peritoneal cavity. We present pathology findings, including ultrastructural features.

Topics: Abdominal Wall; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Intestinal Neoplasms; Keratins; Middle Aged; Osteosarcoma; Peritoneal Neoplasms; Tomography, X-Ray Computed

We report the case of a sarcomatoid carcinoma with a rhabdoid tumor component originating in the gallbladder, along with immunohistochemical and electron microscopic findings. A 61-year-old woman presented with a 5-month history of right upper quadrant pain. Ultrasonography and a computed tomographic scan indicated gallbladder cancer. She underwent a cholecystectomy and a common bile duct resection. A firm mass (4.5 cm in greatest dimension) was present in the neck portion of the gallbladder. The mass was firm, solid, yellowish gray, and granular with areas of necrosis. Microscopically, the tumor was a biphasic sarcomatoid carcinoma and consisted of diffusely arranged pleomorphic cells, focally showing rhabdoid features and neoplastic glands with focal mucin production. Heterologous components such as osteoid, chondroid, and rhabdomyoblastic elements were not identified. By immunohistochemical staining, we demonstrated that the rhabdoid cells coexpressed cytokeratin and vimentin. On electron microscopic examination, the rhabdoid tumor cells showed cytoplasmic whorls of intermediate filaments in the cytoplasm and eccentric nuclei. Two months postoperatively, the follow-up computed tomographic scan showed multiple intrahepatic metastases and omental seedings.

Topics: Carcinosarcoma; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Middle Aged; Rhabdoid Tumor; Vimentin

Hepatobiliary cystadenoma and cystadenocarcinoma of the gall bladder have rarely been reported. An 88-year-old Japanese man was admitted to our clinic because of hypochondralgia and jaundice. Imaging techniques revealed hemobilia and a multilocular cystic tumor in the fundus of the gall bladder, and cholecystectomy was performed. Grossly, the tumor (3.5 x 3 x 3 cm) was multicystic, containing seromucous fluid. The tumor was located in the fibromuscular layer and subserosa of the gall bladder fundus, and protruded into the serosal surface, not into gall bladder lumen. The mucosa appeared free of tumor involvement, and no gall stones were recognized. Microscopically, the tumor was located in the fibromuscular layer, subserosa and tiny focus of the mucosal surface. The tumor consisted of mucin-rich benign columnar cells, dysplastic mucous cells, malignant papillotubular cells and invasive carcinoma cells. Malignant and atypical tumor cells were located in the center of the tumor and in the tiny area of the mucosal surface, while benign tumor cells were located in the peripheral portions of the tumor and in the serosal side. Neither ovarian stroma-like mesenchymal stroma nor an oncocytic change in tumor cells was recognized. Non-tumorous gall bladder showed chronic cholecystitis. Immunohistochemically, benign and carcinoma cells were positive for cytokeratins, epithelial membrane antigen, CA19-9, MUC1, MUC5AC and MUC6, and carcinoma cells were also positive for carcinoembryonic antigen and p53 protein. The present case indicates that hepatobiliary cystadenocarcinoma without mesenchymal stroma may occur in the gall bladder of old men, and suggests that hepatobiliary cystadenoma without mesenchymal stroma may transform into hepatobiliary cystadenocarcinoma in the gall bladder.

Topics: Aged; Aged, 80 and over; Biliary Tract Neoplasms; CA-19-9 Antigen; Carcinoembryonic Antigen; Cystadenocarcinoma; Cystadenoma; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Mucin 5AC; Mucin-1; Mucin-6; Mucins; Tumor Suppressor Protein p53

We describe a case of benign signet ring cell change in the gallbladder mucosa. On histopathological examination of H&E-stained sections, the gallbladder epithelium showed multilayering. The epithelial cells were large, columnar to polygonal with a small round basal or eccentric nucleus and vacuolated cytoplasm, giving them a signet ring appearance. There was no nuclear atypia, hyperchromatism or mitotic activity. The cells showed uniform positivity with mucicarmine, PAS and Alcian blue stains. The cytoplasmic vacuolations were negative for fat stains (Oil red O and Sudan IV). On immunohistochemistry, the cells showed positivity with antibodies for pancytokeratin (PCK) and epithelial membrane antigen (EMA). A diagnosis of benign signet ring cell change with multilayering in the gall bladder mucosa was made. Thoroughly reviewing the literature, we found only one case of benign signet ring cell aggregates in the gallbladder mucosa documented earlier. The lesion is hereby reported because of the unique histomorphology and the diagnostic dilemma which can occur as a malignant change in situ has to be excluded.

Topics: Adult; Carcinoma, Signet Ring Cell; Cholecystectomy; Diagnosis, Differential; Epithelium; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; Mucous Membrane

Expression of cytokeratins 7 (CK7) and 20 (CK20) may help distinguish the site of origin for metastatic carcinomas. Little is known regarding their expression in biliary tract and pancreatic carcinomas. Our aim was to study the expression of CK7 and CK20 in these tumors.. Fifty-three carcinomas of the extrahepatic bile ducts (n = 8), ampulla of Vater (n = 7), gallbladder (n = 11), and pancreas (n = 27), were retrieved from the surgical pathology files of the University of Massachusetts Medical Center. Formalin-fixed, paraffin-embedded sections were immunostained with mouse monoclonal antibodies to CK7 and CK20 using an avidin-biotin immunoperoxidase technique with microwave antigen retrieval. The percentage of cells positive for each antibody was assessed on a scale of 0 to 3 (0, <10%; 1+, 10% to 50%; 2+, 51% to 90%; 3+, >90%).. The majority of carcinomas in all groups were positive for CK7 (CK7+) and negative for CK20 (CK20-). Of the CK7+ tumors, the majority of tumors in each group were 3+ positive.. (1) Carcinomas of the extrahepatic biliary tract and pancreas are strongly positive for CK7 and negative for CK20 and can be included in the differential diagnosis of other carcinomas with this profile in metastatic sites. (2) The CK7/CK20 immunostaining profile will not identify the site of origin for tumors with extensive growth in the porta hepatis region.

Topics: Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Carcinoma; Diagnosis, Differential; Female; Gallbladder Neoplasms; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Pancreatic Neoplasms

We evaluated the cytokeratin profile of intrahepatic cholangiocarcinoma with respect to its histological classification and intrahepatic location (peripheral vs. hilar), and compared its profile with that of a variety of metastatic adenocarcinomas in liver.. Expression of cytokeratins 7, 8, 18, 19 and 20 was immunohistochemically examined in intrahepatic cholangiocarcinoma (n = 77) and metastatic adenocarcinoma in liver (21 colorectal, 14 gastric, three gallbladder and three pancreatic cancers). Materials were autopsy or surgical specimens. Cytokeratins 7, 8, 18 and 19 were expressed in 75 (97%), 75 (97%), 59 (77%) and 71 (92%) cases of intrahepatic cholangiocarcinoma, respectively. Moderate and extensive expression of cytokeratin 18 was more frequent in the peripheral than in the hilar type. Moderate and extensive expression of cytokeratin 19 was seen in almost all cases of well-differentiated intrahepatic cholangiocarcinomas, while expression was decreased relatively in the moderately and decreased more in the poorly differentiated cases. While cytokeratin 20 was not found in non-neoplastic biliary epithelia or in well-differentiated intrahepatic cholangiocarcinomas, this cytokeratin was occasionally detectable in moderately and poorly differentiated intrahepatic cholangiocarcinomas and its expression was more frequent in the hilar type. Cytokeratin 20 expression was observed in 17 (81%) of metastatic adenocarcinomas in liver from colorectal regions, to a lesser degree in those from gastric regions, and was rare in those from gallbladder and pancreatic regions; cytokeratin 7 showed a reverse expression pattern in these metastatic adenocarcinomas in liver. The profile of cytokeratins 7 and 20 of metastatic colorectal and gastric carcinomas differed from that for intrahepatic cholangiocarcinomas, while that of metastatic gallbladder and pancreatic carcinoma was similar to that for intrahepatic cholangiocarcinomas. Moreover, cytokeratin 18 and 19 expression was significantly infrequent in metastatic gastric carcinomas than in intrahepatic cholangiocarcinomas and metastatic colorectal carcinomas.. The combined immunostaining of cytokeratins 7, 18, 19 and 20 is useful for the characterization of intrahepatic cholangiocarcinomas with respect to histological subtypes and intrahepatic location. It helps to differentiate intrahepatic cholangiocarcinoma from metastatic adenocarcinomas in liver and from colorectal and gastric regions; it also indicates the primary focus metastatic adenocarcinomas in livers.

Topics: Adenocarcinoma; Biomarkers; Cholangiocarcinoma; Colorectal Neoplasms; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms

Metastatic adenocarcinoma in the liver with an unidentified primary tumor site is a common clinical problem. Pathologists often are asked to identify the primary tumor site. The histologic picture itself usually is not helpful, because the histology may be similar in the metastases of tumors with different primary localizations. Immunohistochemistry can be helpful, but the previously recommended antibody panels are too complicated for everyday use.. A simple immunohistochemical algorithm with two monoclonal cytokeratin (CK) antibodies, CK20 and CK7, was tested on 93 autopsy cases of adenocarcinomas metastatic to the liver. Sections of the liver metastases were stained automatically and evaluated as negative (no staining), focally positive, or diffusely positive. Statistical comparison of the staining results for a single antibody was calculated as an odds ratio.. Thirty-six of 93 (39%) metastases proved to be CK20 positive (+). In this group, the CK20+/CK7 negative (-) pattern was highly characteristic for colorectal localization of the primary tumor, having been observed 17 of 21 of the cases (81%). The CK20+/CK7+ pattern of the metastatic liver adenocarcinomas was highly suggestive of primary localization in the pancreas or biliary tract (11 of 14 cases; 79%). Exclusion of the tumors originating in the stomach raised these values to 94% and 92%, respectively. The statistically calculated predicted probability of primary tumor site being in the colon or rectum for CK20+/CK7- metastasis was 78,41%, the probability of a primary tumor being located in the pancreas or biliary tract was 74,85%, if calculated for the whole study group.. The tested simple algorithm proved to be useful in CK20 positive (+) cases, predicting a primary tumor localization in the colon, rectum, pancreas, or biliary tract with high accuracy. The CK20- group was too heterogeneous to be classified adequately by these two antibodies.

Topics: Adenocarcinoma; Algorithms; Colorectal Neoplasms; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Liver Neoplasms; Male; Neoplasms, Unknown Primary; Pancreatic Neoplasms; Retrospective Studies; Stomach Neoplasms

The histological detection of lymph node metastasis in patients with gallbladder carcinoma is of major prognostic significance. However, it may be difficult to identify nodal involvement by conventional pathological examination of hematoxylin-eosin (HE)-stained sections when metastases are of microscopic size. In the present study, an attempt was made to detect lymph node metastasis precisely from gallbladder carcinoma, even by low-power microscopic examination, using immunohistochemistry with an anti-cytokeratin antibody.. A total of 431 lymph node specimens dissected during surgery from 33 patients with carcinoma of the gallbladder were investigated. A pair of mirror-image sections were obtained from each of the dissected lymph nodes and then stained using standard HE and immunohistochemical methods utilizing a monoclonal antibody against cytokeratin 7. The HE- and immunohistochemically stained sections were examined for the presence of tumor cells using light microscopy.. All 78 lymph nodes from 12 patients with early gallbladder carcinoma were negative for both HE- and cytokeratin-positive cancer cells. Of 353 lymph nodes from 21 patients with advanced gallbladder carcinoma, HE staining showed that 98 were metastasis-positive. Among these 98 lymph nodes, 95 (97%) proved to be positive for metastasis based on cytokeratin immunostaining. On the other hand, the remaining 255 lymph nodes were cancer-free on the basis of HE staining results. Of the 255 HE-negative lymph nodes, seven (2.7%) were found to be positive for micrometastasis on the basis of cytokeratin staining.. Cytokeratin staining of dissected lymph nodes is a useful new diagnostic tool for detecting micrometastatic foci in regional lymph nodes of patients with gallbladder carcinoma.

Topics: Adult; Aged; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged

We describe three cases of benign signet-ring cell aggregates in the colon associated with pseudomembranous colitis, adenomatous polyp of the colon and ulcerated mucosa of the gallbladder excised for gallstones. In all cases, we found loose, benign signet-ring cell aggregates overlying the ulcerated mucosa surface, simulating signet ring-cell carcinoma. The most important sign of the benign signet-ring cell aggregates is that they are always confined to the surface of the mucosa of the intestine or gallbladder mucosa or crypts of the intestinal epithelium. In no case did we see an invasion of these cells into the lamina propria of the mucosa. In all cases, the benign signet-ring cell aggregates were immunohistochemically positive with antibodies to cytokeratins. The occurrence of benign signet-ring cell aggregates is a rare and very misleading diagnostic pitfall which must be differentiated from signet-ring cell carcinoma of the colon and gallbladder.

Topics: Adenomatous Polyps; Carcinoma, Signet Ring Cell; Colonic Neoplasms; Diagnosis, Differential; Enterocolitis, Pseudomembranous; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Intestinal Mucosa; Keratins; Male; Middle Aged

Although vascular invasion is common in many malignant tumors, disseminated intravascular anaplastic neoplasms with occult primary tumor are rare occurrences. Intravascular malignant lymphoma, also called angiotropic lymphoma, is a rare variant of large cell lymphoma predominantly involving vessels in multiple organs, and usually without significant nodal involvement. Although initially misinterpreted as an endothelial neoplasm-angioendotheliomatosis-immunohistochemical studies subsequently proved it to represent a peculiar form of malignant lymphoma. In this report, we describe two patients with extensive intravascular dissemination of angiosarcoma initially without clinically obvious primary tumor. These may be interpreted as examples of true angioendotheliomatosis. In each case the immunohistochemical studies ruled out the most common intravascular malignant neoplasms. The diagnosis of intravascular angiosarcoma was confirmed by the immunoreactivity of the tumor cells to several markers of endothelial lineage in both cases. Thus, angiosarcoma may present with intravascular dissemination and occult primary tumor and closely resemble metastatic carcinoma, melanoma, or angiotropic lymphoma. Immunohistochemical studies are crucial in ruling out these possibilities and in confirming the endothelial origin of the neoplastic cells.

Topics: Adult; Aged; Biomarkers; Biopsy; Diagnosis, Differential; Fatal Outcome; Female; Gallbladder Neoplasms; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Liver Neoplasms; Lung Neoplasms; Platelet Endothelial Cell Adhesion Molecule-1; Vascular Neoplasms; von Willebrand Factor

Primary carcinoma of the gallbladder is a rare neoplasm that is frequently difficult to diagnose preoperatively. The obstacles to diagnosis include vague symptoms and the relative inaccessibility of the gallbladder and cystic duct to biopsy. Cytological descriptions of gallbladder carcinoma are sparse and are largely confined to malignant cells identified in aspirated bile. Examination of bile is a fairly insensitive technique for diagnosing carcinoma, partially due to the degradative effect of biliary salts on cellular morphology. In the following, we report the findings of three cases of primary carcinoma of the gallbladder examined by fine-needle aspiration cytology.

Topics: Aged; Aged, 80 and over; Biopsy, Needle; Female; Follow-Up Studies; Gallbladder Neoplasms; Humans; Keratins; Male; Tomography Scanners, X-Ray Computed

Three cases of malignant clear cell carcinoma of the gallbladder were studied immunohistochemically with a broad panel of antibodies, especially cytokeratins, in order to better characterize their histogenesis. The advantage of immunohistochemistry in the differential diagnosis between clear cell carcinoma of the gallbladder and other clear cell carcinomas metastatic to the gallbladder such as renal cell carcinoma is discussed.

Topics: Adenocarcinoma, Clear Cell; Aged; Diagnosis, Differential; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged

Gallstone disease remains a leading cause of morbidity and mortality in humans. Despite extensive research into the physiology of the gallbladder, little is known about mucosal events that precede and contribute to stone formation. Here, we describe and partially characterize a cultured epithelial model of human gallbladder mucosa.. Cells originally obtained from a well-differentiated gallbladder mucosal carcinoma were cultured in modified Eagle's minimum media (supplemented with fetal calf serum and antibiotics) on polycarbonate supporting matrices.. Cell cultures were observed to come to confluence with 6 to 9 days. Light and transmission electron microscopy demonstrated the resultant epithelia to be predominantly one cell thick, to be polar in orientation, and to have apical villi. Epithelia exhibited cytokeratin markers consistent with their epithelia origin, functionally acidified the mucosal bathing solutions, and secreted mucin. Further experiments demonstrated transepithelial potential differences, mucosal-to-serosal transfer of sodium which could be inhibited with amiloride and 4-acetamido-4'-isothiocyanatostilbene-2-2'-disulfonic acid, and paracellular movement of neutral molecular probes inversely related to size.. This culture model of human gallbladder mucosal carcinoma cells exhibits parameters consistent with native gallbladder and may offer a convenient new research tool for the study of the pathophysiology of gallstone formation.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; Amiloride; Biological Transport; Disease Models, Animal; Epithelium; Gallbladder; Gallbladder Neoplasms; Humans; Keratins; Methods; Microscopy, Electron; Mucins; Mucous Membrane; Sodium; Tumor Cells, Cultured

A case of adenoendocrine cell carcinoma of the gallbladder with adenomucous cells and neuroendocrine cells is reported. A histochemical and immunohistochemical study revealed that the primary tumor in the gallbladder was composed of mucus-secreting and/or argyrophil cells. Furthermore, the tumor showed a positive reaction to carcinoembryonic antigen (CEA) in all tumor cells, to chromogranin A and cytokeratin in many tumor cells, to endocrine granule constituent (EGC) in some tumor cells, and to serotonin and somatostatin in a few tumor cells. In addition, a few mucous cells showed argyrophilia and EGC-positivity in their cytoplasms. This case suggests that the adenoendocrine cell tumor is derived from endodermal stem cells as a result of bidirectional (exocrine and endocrine) differentiation.

Topics: Adenocarcinoma; Aged; Carcinoembryonic Antigen; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Neurosecretory Systems

A 58-year-old man was seen with obstructive jaundice and discomfort in the upper abdomen. Computed tomographic and ultrasound examinations revealed a soft-tissue mass in the gallbladder. Cholecystectomy and choledochotomy revealed a soft black mass in the gallbladder and a second one in the intrapancreatic portion of the common bile duct. Each was diagnosed as malignant melanoma. Subsequently, a Whipple resection of the pancreas, duodenum, and distal bile duct revealed a melanoma circumferentially invading and obstructing the distal common duct. No lymph node or distant metastasis was identified. Repetitive searches for another primary site have been negative. The tumor apparently originated in the biliary tract. The patient remains almost well 2 years after diagnosis.

Topics: Bile Duct Neoplasms; Common Bile Duct; Gallbladder Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Male; Melanoma; Middle Aged; S100 Proteins; Tomography, X-Ray Computed

Three cases of tubular adenoma of the gallbladder with squamoid spindle cell metaplasia are reported. Two of the three patients, who were middle-aged Japanese, had a solitary polyp in the gallbladder, and the other had three polyps. All the lesions were detected incidentally by ultrasonography. The polyps were pedunculated with a fine or frail stalk, and ranged from 0.5 to 3.9 cm in diameter. Histologically, they were tubular adenomas accompanied by scattered foci composed of a compact collection of short-spindle or oval cells with mild atypia. These cells did not retain intercellular bridges, and lacked intracellular keratinization. Immunohistochemically, the spindle cells stained positively for high-molecular-weight cytokeratin (EAB 903, a marker of squamous cell differentiation), whereas adenoma cells lining the tubules were negative for this antigen. Therefore, the spindle cell component is considered to represent squamoid metaplasia of adenoma cells.

Topics: Adenoma; Adult; Female; Gallbladder Neoplasms; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Male; Metaplasia; Middle Aged; Molecular Weight

Immunohistochemical staining of cell lines derived from human liver tumours showed that five cell lines derived from hepatocellular carcinoma (HCC) and hepatoblastoma were stained positively with monoclonal keratin antibodies, CK-5 (Ker-18-specific) and KL-1 (broad specificity), but not with CK-7 (Ker-7-specific). On the other hand, four carcinoma cell lines derived from the biliary system were stained positively with not only CK-5 and KL-1, but also CK-7.

Topics: Albumins; Alkaline Phosphatase; alpha-Fetoproteins; Antibodies, Monoclonal; Bile Duct Neoplasms; Biomarkers, Tumor; Carcinoma; Carcinoma, Hepatocellular; Gallbladder Neoplasms; Humans; Keratins; Liver Neoplasms; Neoplasm Proteins; Tumor Cells, Cultured

Immunohistochemical studies on synovial sarcomas have proved the potentiality of these neoplasm for epithelial and mesenchymal differentiation and antibodies detecting epithelial cells have been found to be helpful in determining the histological types. In this study different epithelial markers directed against various cytokeratins, HMFG-2 and EMA were investigated on paraffin embedded tissues of 13 cases of synovial sarcomas, with regard to their reliability in unmasking the epithelial components demonstrable in this type of neoplasm. The results lead to three conclusions: firstly, synovial sarcomas possess the capacity for generating different epithelial cell types with uncommon compositions of intermediate filaments as well as of membrane proteins, secondly, these features may be expressed in a heterogenous pattern even within the same tumour and finally, the use of wide range anti-cytokeratin antibodies covering the spectrum of basic as well as acidic type proteins seems to be necessary for the detection of all epithelial components demonstrable in synovial sarcomas.

Topics: Antibodies; Biomarkers, Tumor; Breast Neoplasms; Epithelium; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Sarcoma, Synovial; Skin Neoplasms; Stomach Neoplasms; Synovial Membrane

A case of adenosquamous carcinoma of the gallbladder showing extensive spindle transformation is presented. By light microscopy, areas showing interwoven fascicles of fusiform, poorly differentiated cells closely resembling a sarcoma were seen to merge imperceptibly with areas showing more obvious glandular and squamous cell features. Immunocytochemistry utilizing tissue-specific antibodies against intermediate filaments demonstrated the exclusive presence of prekeratin antibodies in both components of the tumour, thus establishing the epithelial nature of this neoplasm. The importance of immunological phenotyping in the differential diagnosis of epithelial tumours of the gallbladder showing pseudosarcomatous features is underscored.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Female; Gallbladder Neoplasms; Humans; Keratins; Middle Aged

Immunoperoxidase staining for human keratin proteins was performed cytologically on samples from 90 patients with malignant tumors, and histologically on samples from 164 patients with malignant tumors. At the cytological level, almost all tumor cells not only in squamous cell carcinoma but also in nonsquamous cell carcinoma were positive for keratin proteins, in contrast with the apparent abscence of keratin proteins in sarcoma. At the histological level, almost all neoplastic cells of squamous cell carcinoma were positive for keratin proteins, the same as at the cytological level. In contrast, among cases of nonsquamous cell carcinoma, the frequency of appearance of keratin proteins varied according to the organ; it tended to be low in tumors with relatively good prognosis, such as carcinomas in the digestive system or thyroid cancer, and to be high in tumor with poor prognosis, such as pulmonary cancer, gallbladder cancer and endometrial cancer. However, there was a marked difference between the frequency of appearance of keratin proteins at the cytological level and that at the histological level, particularly in the cases of gastric cancer.

Topics: Antibodies; Breast Neoplasms; Colonic Neoplasms; Female; Gallbladder Neoplasms; Histocytochemistry; Humans; Keratins; Lung Neoplasms; Neoplasms; Sarcoma; Stomach Neoplasms; Thyroid Neoplasms; Uterine Neoplasms