bromochloroacetic-acid and Common-Bile-Duct-Neoplasms

We report on a 61-year-old Japanese male with a pedunculated tumor in the common bile duct. The tumor consisted of two types of neoplastic cells. The majority showed atypical spindle- and giant-shaped features and proliferated densely in an inflammatory stroma, revealing a sarcomatous pattern. They expressed vimentin, KL-1, and CAM5.2. The remaining minority showed glandular and tubular features, occupied only less than 5%, located only in the tumor surface, and expressed wide spectrum keratin, KL-1, CAM5.2, epithelial membrane antigen, AE1/AE3, and carcinoembryonic antigen. CD68-positive osteoclast-like giant cells were also observed. Therefore, the patient was diagnosed as having an undifferentiated carcinoma, spindle and giant cell type.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Carcinoembryonic Antigen; Carcinoma, Giant Cell; Cell Differentiation; Cell Proliferation; Cholangiopancreatography, Magnetic Resonance; Common Bile Duct Neoplasms; Humans; Keratins; Ki-67 Antigen; Male; Middle Aged; Mucin-1; Tomography, X-Ray Computed; Tumor Suppressor Protein p53; Vimentin

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

A 78-year-old Japanese man with undifferentiated carcinoma of the common bile duct is presented. Upon gross examination, the common bile duct was found to be obstructed by a nodule measuring 10 x 10 mm. Microscopically, the nodule was ill-defined and composed of atypical spindle-shaped and pleomorphic tumor cells. The spindle-shaped cells proliferated in a whirled or interlacing pattern simulating a sarcoma, and the pleomorphic tumor cells had abundant eosinophilic cytoplasm and bizarre nuclei. Histochemically, a few tumor cells contained mucosubstances stained with the alcian blue (AB) method in their cytoplasm. Immunohistochemically, the tumor cells were diffusely positive for CAM5.2 and AE1/AE3. The histological diagnosis was undifferentiated carcinoma (spindle cell carcinoma) of the common bile duct. Other than our patient, only four other cases of undifferentiated carcinoma in the extrahepatic bile duct have been reported in the literature.

Topics: Aged; Anion Exchange Protein 1, Erythrocyte; Biomarkers; Carcinoma; Common Bile Duct Neoplasms; Humans; Immunohistochemistry; Keratins; Male

Pancreatic and periampullary carcinoma are aggressive tumours where preoperative assessment is challenging. Disseminated tumour cells (DTC) in the bone marrow (BM) are associated with impaired prognosis in a variety of epithelial cancers. In a cohort of patients with presumed resectable pancreatic and periampullary carcinoma, we evaluated the frequency and the potential prognostic impact of the preoperative presence of DTC, defined as cytokeratin-positive cells detected by immunocytochemistry (ICC).. Preoperative BM samples from 242 patients selected for surgical resection of presumed resectable pancreatic and periampullary carcinoma from 09/2009 to 12/2014, were analysed for presence of CK-positive cells by ICC. The median observation time was 21.5 months. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier and Cox regression analysis.. Successful resections of malignant tumours were performed in 179 of the cases, 30 patients resected had benign pancreatic disease based on postoperative histology, and 33 were deemed inoperable intraoperatively due to advanced disease. Overall survival for patients with resected carcinoma was 21.1 months (95% CI: 18.0-24.1), for those with benign disease OS was 101 months (95% CI: 69.4-132) and for those with advanced disease OS was 8.8 months (95% CI: 4.3-13.3). The proportion of patients with detected CK-positive cells was 6/168 (3.6%) in resected malignant cases, 2/31 (6.5%) in advanced disease and 4/29 (13.8%) in benign disease. The presence of CK-positive cells was not correlated to OS or DFS, neither in the entire cohort nor in the subgroup negative for circulating tumour cells (CTC).. The results indicate that CK-positive cells may be present in both patients with malignant and benign diseases of the pancreas. Detection of CK-positive cells was not associated with differences in prognosis for the entire cohort or any of the subgroups analysed.. clinicaltrials.gov ( NCT01919151 ).

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Biomarkers, Tumor; Common Bile Duct Neoplasms; Duodenal Neoplasms; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Pancreatic Neoplasms; Prognosis; Survival Rate

To investigate immunohistochemical predictors for intestinal and pancreatobiliary types of adenocarcinoma of ampulla of Vater and identify clinicopathological characteristics associated with the histological types and patient survival.. Immunohistochemical markers included MUC1, MUC2, MUC5AC, CDX2, CK7, and CK20. The data were analyzed by univariate and multivariate methods. The two-step cluster method was used to determine the best immunohistochemical markers to discriminate the intestinal from the pancreatobiliary type.. This study identified 9 (33.3%) intestinal and 21 (66.7%) pancreatobiliary tumors. CK7 and CDX2 achieved the highest value (= 1) as predictor markers, while CK20, MUC1, and MUC2 showed degrees of importance equal to 0.77, 0.71, and 0.68, respectively. MUC5AC did not reach 0.50 of importance. In the univariate analysis, lymph node involvement, staging (TNM), and angiolymphatic and perineural invasions were associated with histological types. The independent clinicopathological variable in the multivariate model to predict the histological type was angiolymphatic invasion (p = 0.005), OR = 17 (95% CI 2.33 to 123.83). The final model showed positive nodes (N1) associated with shorter survival (HR = 9.5; p = 0.006). Overall survival at 12, 36, and 60 months was 88.5, 67.0, and 47.6%, respectively.. CDX2 and CK7 were the immunohistochemical markers that best discriminated the intestinal from the pancreatobiliary type. Lymph node involvement had a high impact on survival and proved to be more frequent in the pancreatobiliary type.

Topics: Adenocarcinoma; Adult; Aged; Ampulla of Vater; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; CDX2 Transcription Factor; Common Bile Duct Neoplasms; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucins; Neoplasm Proteins; Prognosis

Subclassification of ampullary adenocarcinomas into intestinal and pancreatobiliary type has prognostic and therapeutic implications. Immunohistochemical staining against specific biomarkers has been proven to be a useful adjunct in determining the exact histotype. Furthermore the immunohistochemical profile is suggestive of the molecular pathogenic mechanisms through which the tumor evolved. The aim of this study was to correlate p53, MDM2, CK7, CK20, MUC1, MUC2 and CDX2 expression in ampullary adenocarcinomas with the type of differentiation and patients' survival.. Forty-seven radically resected ampullary adenocarcinomas were included in this study. Thirty-eight of them were eligible for survival analysis. Patients' data were retrospectively collected. All tumors were classified as intestinal or pancreatobiliary type, according to histologic criteria, and immunohistochemically stained against the aforementioned markers.. There were 18 intestinal and 29 pancreatobiliary type ampullary adenocarcinomas. A trend was found between intestinal type tumors and large tumor size. CK20, MUC2 and CDX2 expression was more prevalent in intestinal type tumors, while MUC1 was more frequently expressed in pancreatobiliary type tumors. Neither p53 nor MDM2 differential expression between the two histotypes reached statistical significance. Multivariate analysis indicated CK20 and MUC1 as independent predictors of the histotype. Mean and median survival was 90.3 and 55 months respectively. Overall 5-year survival rate was 48%. Survival analysis indicated TNM stage as the only independent prognostic factor. Although significant difference in survival rates among the two histotypes was implied based on survival plots, this difference could not gain statistical significance.. Immunoreactivity against CK20 and MUC1 in ampullary carcinomas is a useful adjunct to histologic examination in determining histotype. None of the immunohistochemical markers studied has prognostic significance. Future studies focused on other signaling pathways should seek further evidence of distinct tumorigenic mechanisms between histotypes of ampullary adenocarcinoma.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Biomarkers, Tumor; CDX2 Transcription Factor; Cell Differentiation; Common Bile Duct Neoplasms; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Male; Middle Aged; Mucins; Prognosis; Proportional Hazards Models; Proto-Oncogene Proteins c-mdm2; Tumor Suppressor Protein p53; Young Adult

Topics: Adenocarcinoma; Carcinoid Tumor; Child; Chromogranin A; Common Bile Duct; Common Bile Duct Neoplasms; Diagnosis, Differential; Duodenum; Gallbladder; Humans; Keratins; Lymphoma; Male; Mucin-1; Neoplasm Invasiveness; Rhabdomyosarcoma; Stomach; Synaptophysin

Topics: Abdominal Pain; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Common Bile Duct Neoplasms; Female; Humans; Jaundice, Obstructive; Keratins; Leukemia, Myeloid, Acute; Middle Aged; Peroxidase; Proto-Oncogene Proteins c-kit; Pruritus; Sarcoma, Myeloid; Vimentin

Topics: Carcinosarcoma; Common Bile Duct Neoplasms; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Vimentin

This study aimed to clarify the clinical significance of lymph node micrometastasis in ampullary carcinoma.. Pancreaticoduodenectomy with regional lymphadenectomy was performed for 50 consecutive patients with ampullary carcinoma. A total of 1,283 regional lymph nodes (median, 25 per patient) were examined histologically for metastases. Overt metastasis was defined as metastasis detected during routine histologic examination with hematoxylin and eosin. Micrometastasis was defined as metastasis first detected by immunohistochemistry with an antibody against cytokeratins 7 and 8. The median follow-up period was 119 months after resection.. Overt metastasis was positive in 90 lymph nodes from 27 patients. Micrometastasis was positive in 33 lymph nodes from 12 patients, all of whom also had overt nodal metastases. Patients with nodal micrometastasis had a larger number of lymph nodes with overt metastasis (median, 3.5) than those without (median, 0; P<0.001). Overt metastasis to distant nodes (superior mesenteric nodes, para-aortic nodes) was more frequent (P=0.001 and P=0.038, respectively) in patients with nodal micrometastasis. Nodal micrometastasis was found to be a strong independent prognostic factor on univariate (P<0.0001) and multivariate (relative risk, 5.085; P=0.007) analyses. From among the 27 patients with overt nodal metastasis, the outcome after resection was significantly worse in the patients with nodal micrometastasis (median survival time of 11 months) than in those without (median survival time of 63 months; P=0.0009).. Immunohistochemically detected lymph node micrometastasis indicates intensive lymphatic spread, and thus adversely affects the survival of patients with ampullary carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Ampulla of Vater; Biomarkers, Tumor; Common Bile Duct Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Pancreaticoduodenectomy; Prognosis; Survival Rate

Pancreatobiliary and ampulla of Vater adenocarcinomas frequently metastasize to regional lymph nodes, liver, or lung and are difficult to diagnose because they lack specific immunohistochemical markers. We studied the expression of cytokeratin 7 (CK7), cytokeratin 17 (CK17), cytokeratin 20 (CK20), CDX2, mucin 1 (MUC1), mucin 2 (MUC2), and mucin 5AC (MUC5AC) in 46 cases of pancreatic ductal carcinoma, 18 ampulla of Vater adenocarcinomas, and 24 intrahepatic cholangiocarcinomas. The expression of MUC1 and CK17 was restricted to pancreatic ductal carcinoma (41 of 46, 89%; 38 of 46, 83%, respectively), the ampullary carcinoma of pancreatobiliary origin (6 of 6, 100%; 5 of 6, 83%, respectively), and intrahepatic cholangiocarcinoma (20 of 24, 83%; 17 of 24, 71%, respectively). More than 50% of cases of pancreatobiliary adenocarcinomas showed diffuse cytoplasmic CK17 positivity. In contrast, less than 5% cases (8 of 184) of extra-pancreatobiliary nonmucinous adenocarcinomas expressed CK17, and only 3 of them showed diffuse CK17 positivity. The expression of MUC2 and CDX2 was restricted to the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin (9 of 11, 82%; 11 of 11, 100%, respectively). MUC2 was rarely expressed in pancreatic ductal carcinoma (1 of 46, 2%) and was negative in the ampullary carcinoma of pancreatobiliary origin and in intrahepatic cholangiocarcinoma. A heterogeneous CDX2 staining pattern was seen in 1 of 6 cases of the ampullary carcinoma of pancreatobiliary origin (17%), 5 of 24 intrahepatic cholangiocarcinomas (21%), and 10 of 46 (22%) pancreatic ductal carcinomas. In contrast, all 11 cases of the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin showed homogeneous CDX2 nuclear positivity. We concluded that CK17 is a useful marker in separating pancreatobiliary adenocarcinomas from extra-pancreatobiliary nonmucinous adenocarcinomas, including adenocarcinomas from the colon, breast, gynecologic organs, stomach, lung, prostate, thyroid, kidney, and adrenal gland, and malignant mesothelioma. MUC1+/CK17+ can be used as positive markers for pancreatic ductal carcinomas, the ampullary carcinoma of pancreatobiliary origin, and cholangiocarcinomas with positive predictive values of 76%, 83%, and 58%, respectively. MUC2+/CDX2+ can be used as positive markers for the intestinal-type adenocarcinoma of duodenal papillary origin with a positive predictive value of 82%.

Topics: Adenocarcinoma; Ampulla of Vater; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; CDX2 Transcription Factor; Cholangiocarcinoma; Common Bile Duct Neoplasms; Female; Homeodomain Proteins; Humans; Immunohistochemistry; Keratins; Male; Mucins; Neoplasm Proteins; Pancreatic Neoplasms

A broad histomorphologic spectrum of ampullary carcinomas of Vater make a reproducible histologic classification difficult. Using cytokeratin immunohistochemistry, we present a new classification of ampullary carcinomas and analyze their clinical significance. Fifty-five invasive carcinomas of Vater's ampulla were histologically classified into pancreaticobiliary, intestinal, and other types. Serial sections of all carcinoma specimens were additionally stained with antibodies to cytokeratins (CK7, CK20), apomucins (MUC1, MUC2, MUC5AC), CEA, CA19-9, Ki67, and p53. Follow-up of patients from 4 months to 22 years after surgery (mean interval, 51.6 months) was evaluated. Most carcinomas of the ampulla of Vater were of immunohistochemically pancreaticobiliary type (iPT, CK7+, CK20-; 54.5%) or intestinal type (immunohistochemically intestinal type [iIT], CK7-, CK20+; 23.6%). Some carcinomas of immunohistochemically "other" type (iOT both CK7+ and CK20+ or CK7- and CK20-; 21.8%) had precursor lesions of iIT or iPT. Carcinomas positive for MUC2 or CEA were associated with iIT (MUC2, P < 0.001; CEA, P = 0.003), whereas MUC5AC-positive carcinomas were related to iPT (P = 0.005). Our classification based on cytokeratin-immunohistochemistry correlated well with the histologic classification according to published criteria (kappa-coefficient = 0.398; P < 0.001). Furthermore, histologically unusual types could be histogenetically related to pancreaticobiliary duct mucosa or intestinal mucosa. Therefore, all 4 signet-ring cell carcinomas were iIT carcinomas. Thus, cytokeratin immunohistochemistry allows a reproducible, histogenetically based categorization of ampullary carcinomas. However, neither histopathologic nor immunohistochemical subgroups significantly correlated with clinical outcome in our German collective. The overall survival was significantly shorter in males (P = 0.032) and patients with positive nodal stage (N1 < N0; P = 0.0025).

Topics: Aged; Ampulla of Vater; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Signet Ring Cell; Common Bile Duct Neoplasms; Female; Follow-Up Studies; Gastric Mucins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Ki-67 Antigen; Male; Middle Aged; Mucin 5AC; Mucin-1; Mucin-2; Mucins; Neoplasm Staging; Tumor Suppressor Protein p53

Ampullary carcinomas (AC) account for 33% of all surgically operable pancreatoduodenal tumors. The 5-year relative survival rate is 50% and tumoral stage is the main prognostic factor. However, among the three AC histological subtypes (intestinal, pancreatobiliary and mixed), a favorable prognostic has been reported for the intestinal subtype.. The aims of this study were to determine the prognostic impact of AC histologic subtype and of cytokeratins (CK) 7 and 20 immunostaining profile in these tumors.. Clinical data of 54 AC were obtained retrospectively. Macroscopic and histologic documents were reviewed and immunostainings for CK7 and CK20 were performed.. The classification of tumors, according to histological subtype, was: intestinal 26%, pancreatobiliary 65% and mixed 9%. No correlation was found between histological subtype and tumor stage. The 5-year survival rate varied from 100% for intestinal subtype to 35% for pancreatobiliary subtype. A strong correlation (p < 0.0001) was found between histological subtype and CK7/CK20 immunostaining profile. The 5-year survival rate varied from 100% for CK7-/CK20 + AC to 40% for CK7 + /CK20- AC.. In our study, the intestinal histological subtype had a favorable prognostic value. CK7/CK20 immunostaining profile was helpful for the identification of histological subtype and appears to provide additional prognostic information.

Topics: Adenocarcinoma; Ampulla of Vater; Biomarkers; Common Bile Duct Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Retrospective Studies

Adenomyoma and adenomyomatous hyperplasia of the Vaterian system are consistently benign lesions. Clinically, adenomyoma mimics frequently ampullary adenoma or carcinoma, and biopsy analysis is often difficult. The histogenesis of ampullary adenomyoma and adenomyomatous hyperplasia is still subject to debate. We present a retrospective study of clinicopathological features of 13 cases of surgically resected ampullary adenomyoma. The age of our patients was between 38 and 78 years (mean: 63 y). The preoperative diagnosis was ampullary tumor or tumor of the head of the pancreas. On macroscopy, a white, firm lesion of the ampullary wall was observed; its size ranged between 10 and 30 mm. Histologically the lesion consisted of multiple glandular structures surrounded by a fibroblastic/myofibroblastic proliferation, resulting in a "pseudo-hypertrophy" of the Vaterian system. The immunophenotype of the epithelial component was cytokeratin 7+/cytokeratin 20-, similar to that of the normal biliary and pancreatic duct system. The epithelial cells exhibited low proliferative activity. The hyperplastic myofibroblastic cells expressed smooth muscle actin. A complete pancreatic heterotopy contiguous with the adenomyoma was noted in three cases. Adenomyoma and adenomyomatous hyperplasia of the Vaterian system are benign lesions frequently treated by extensive surgery because of long-term biliary obstruction. The clinicopathological characteristics suggest either a reactive and/or a malformative, nonneoplastic nature for this lesion, which could, in some cases, develop from heterotopic pancreas. The immunophenotype of epithelial cells may be a useful tool for differentiating it from ampullary adenoma on biopsy specimens.

Topics: Adenomyoma; Adult; Aged; Ampulla of Vater; Biomarkers, Tumor; Common Bile Duct Neoplasms; Female; Humans; Hyperplasia; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Pancreaticoduodenectomy; Retrospective Studies; Treatment Outcome

We studied reactivity of cytokeratins (CK) 7, 17, and 20 in 64 pancreaticobiliary adenocarcinomas to examine the effect of different cut-point thresholds on "positive" results, compare ampulla of Vater and pancreas adenocarcinomas, and provide additional experience with CK17 reactivity. Almost all neoplasms had extensive CK7 reactivity. The number of CK20-positive cases decreased from 29 (45%; any stained cells) to 19 (30%; > 25% staining) to 14 (22%; > 50% staining) with an increasing threshold of reactive cells. Similar shifts in the distribution of CK7 and CK20 reactivity occurred when different thresholds of reactivity were used for a positive result. There were no differences in CK7 or CK20 reactivity in pancreas only, ampulla only, and neoplasms involving both sites. Of 64 adenocarcinomas, 29 (45%) had no or single-cell CK17 reactivity, and 19 (30%) had reactivity in more than 50% of neoplastic cells. Ampulla of Vater and pancreas adenocarcinomas have similar CK immunophenotypes that cannot assist in distinguishing ampullary from pancreatic neoplasms on endoscopically procured tissue. CK17 staining occurs in approximately 50% of pancreaticobiliary adenocarcinomas and is usually patchy. Single antibody staining results, especially CK7 and CK20 coordinate reactivity, are influenced by the reactivity threshold used.

Topics: Adenocarcinoma; Ampulla of Vater; Biomarkers, Tumor; Cell Count; Common Bile Duct Neoplasms; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Pancreatic Neoplasms

Based on the fact that pancreatic carcinoma is still associated with poor outcome, the aim of the study was to determine frequency of early tumor cell dissemination using immunohistology in lymph nodes classified as tumor-free by conventional histopathology.. Fifteen patients with ductal pancreatic carcinoma and 10 patients with carcinoma of the papilla of Vater underwent radical tumor resection (resection status R0, tumor staging pTxpN0M0). In total, 229 lymph nodes classified as tumor-free by histopathology were investigated for disseminated tumor cells using antibodies against cytokeratin and CA19-9. As control, 81 lymph nodes obtained from patients with chronic pancreatitis were analyzed.. In 55 of 229 lymph nodes (26.3%), cytokeratin-positive, disseminated tumor cells were detected. Cytokeratin-positive cells were found in at least one resected lymph node of each patient with ductal carcinoma of the pancreatic head (100%), whereas in patients with carcinoma of the papilla of Vater, no disseminated tumor cells were detected using the antibody against cytokeratin. Similarly, there was no detection of tumor cells (false-positive) in patients with chronic pancreatitis. In contrast, CA19-9 antigen was detectable in resected lymph nodes of each of the 25 carcinoma patients (pancreatic carcinoma and carcinoma of the papilla of Vater). Interestingly, 52 of 81 lymph nodes (64.2%) from the control group (chronic pancreatitis) were false-positive.. Detection of disseminated tumor cells in lymph nodes using an antibody against cytokeratin is specific and suitable while use of an antibody against CA19-9 is not recommendable because of the high rate of false-positive results. The results may indicate that ductal pancreatic carcinoma generates early dissemination of tumor cells into lymph nodes. This may be one explanation for the poor outcome of this carcinoma compared with that of the carcinoma of the papilla of Vater (14 versus 48 months P < 0.05).

Topics: Adenocarcinoma; Adult; Aged; Ampulla of Vater; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoma; Chronic Disease; Common Bile Duct Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Pancreatitis; Predictive Value of Tests; Prognosis

This prospective study aimed to evaluate the detection of micrometastases in bone marrow of patients with suspected pancreatic and ampullary cancer and to determine their predictive value on overall survival.. Between December 1997 and December 1998, 35 patients (19 male, 42-77 years) with suspected pancreatic and ampullary cancer underwent diagnostic laparoscopy as a final staging procedure before exploration. Bone marrow was aspirated from the iliac crest at the beginning of laparoscopy. Mononuclear cells were isolated and stained using the specific monoclonal antibody CAM 5.2.. Cytokeratin-positive cells were detected in 12/35 (34%) of all patients. In the 31 patients with a final diagnosis of carcinoma, a positive staining was found in 10/31 (32%) of the bone marrow aspirates. After a median follow-up of 17 months (2-24), 15/31 (48%) patients had died: 7/10 (70%) with and 8/21 (38%) without micrometastases (* P<0.04). All four patients who turned out to have chronic pancreatitis were alive without malignancy. In two of these four patients, distinct cytokeratin-positive cells were seen.. Micrometastases in bone marrow of patients with the final diagnosis pancreatic or ampullary carcinoma seem to predict a significantly shorter survival. However, clinical use of cytokeratin markers cannot be recommended at present, because false-positive staining was found.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers; Biomarkers, Tumor; Bone Marrow Cells; Bone Marrow Neoplasms; Common Bile Duct Neoplasms; Female; Humans; Immunohistochemistry; Inhalation; Keratins; Laparoscopy; Male; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Prospective Studies; Survival Analysis

Undifferentiated carcinomas with osteoclast-like giant cells are rare pancreatic and periampulary neoplasms that morphologically mimic giant cell tumor of bone. Despite numerous publications based primarily on single case reports, the terminology, histogenesis, and biologic behavior of these tumors remain controversial.. The authors studied one periampullary and nine pancreatic neoplasms of this type. Immunohistochemistry was performed on nine of the cases and clinical follow-up data was obtained in eight.. The neoplasms were large (average 9 cm), partially or completely multicystic, and hemorrhagic. Histologically, they were composed predominantly of ovoid or spindle-shaped bland mononuclear cells and evenly spaced osteoclast-like giant cells. However, three neoplasms had foci in which the nuclear pleomorphism of the mononuclear cells approached that observed in anaplastic spindle and giant cell carcinomas. Other histologic features included phagocytosis of the mononuclear cells by the osteoclast-like giant cells (in 7 of 10 cases), osteoid or bone formation (in 3 of 10 cases), and chondroid differentiation (in 1 of 10 cases). Four neoplasms had foci of conventional adenocarcinoma and two arose in preexisting mucinous cystic neoplasms of the pancreas. The mononuclear cells were positive for epithelial markers in six of nine tumors tested (cytokeratins AE-1, AE-3, Cam 5.2, and/or epithelial membrane antigen). They were negative for the histiocytic markers (CD-68, lysozyme) in all nine cases tested. In contrast, the osteoclast-like giant cells were positive for CD-68 in all nine cases, positive for lysozyme in four cases, and negative for cytokeratins (AE-1, AE-3, and Cam 5.2) in all nine cases. p53 stained the mononuclear tumor cells in three cases and MIB-1 stained the mononuclear tumor cells in four cases, but the osteoclast-like giant cells did not stain with either antibody in all nine cases tested. Most of the patients died of disease within 1 year of diagnosis; only 1 patient was alive and disease free 14 years after surgical excision.. The association of these tumors with conventional adenocarcinoma or mucinous cystic neoplasms, the histologic features, and the immunohistochemical profile supports an epithelial phenotype for the mononuclear cells and a reactive histiocytic lineage for the nonneoplastic osteoclast-like giant cells. These neoplasms, which are better classified as undifferentiated carcinomas, follow an aggressive clinical course; most patients die of disease within 1 year.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoma; Common Bile Duct Neoplasms; Female; Giant Cells; Humans; Immunohistochemistry; Keratins; Macrophages; Male; Middle Aged; Osteoclasts; Pancreatic Neoplasms; Tumor Suppressor Protein p53

We report the clinicopathologic, immunohistochemical, and ultrastructural features of three small-cell neuroendocrine carcinomas of the ampullary region of the duodenum. All patients were men; their ages were 51, 62, and 66 years. The therapy consisted of pancreatoduodenectomy. All patients died of the disease; median survival was 10 months from the diagnosis. The histological appearance was identical to pulmonary and extrapulmonary small-cell carcinoma. The neuroendocrine differentiation was demonstrated ultrastructurally by the presence of dense-core granules, and by the positive immunoreaction for neuron-specific enolase and Leu-7 in each case. One case expressed a focal positivity for chromogranin A (PHE-5) and argyrophilic granules. The same case showed the presence of neurofilaments on frozen material. Neurofilament proteins could not be demonstrated in any case in paraffin sections. Neoplastic cells exhibited cytoplasmic immunostaining for cytokeratins (CAM 5.2) in all cases. In one case, a large number of neoplastic cells (60-70%) exhibited nuclear Ki-67 positivity. We postulate that the disease's histogenesis was from epithelial stem cell expressing both epithelial and neuroendocrine characteristics. The clinical behavior of small-cell neuroendocrine carcinomas of the ampullary region appears to be extremely aggressive, with early metastases and fatal outcome.

Topics: Adenocarcinoma; Aged; Antigens, Differentiation; Antigens, Surface; Carcinoma, Small Cell; CD57 Antigens; Chromogranin A; Chromogranins; Common Bile Duct Neoplasms; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Microscopy, Electron; Middle Aged; Phosphopyruvate Hydratase

A bronchial P cell carcinoid, which was negative for all hormones immunocyto chemically tested, showed a globular intracytoplasmic inclusion in almost every cell. The inclusions were not clearly distinguishable using the haematoxylin- eosin- safran procedure; they were best demonstrated with the Masson trichrome stain and the Grimelius technique and were easily detected in 1 micron thick Epon sections as target-like structures. On electron microscopy, they were found to be composed of filamentous aggregates entrapping a few endosecretory granules, which showed degenerative changes. The filaments, 8-10 nm in diameter, lacked any periodicity; they were randomly dispersed in the central area and arranged in broken concentric swirls at the periphery of the inclusions. The globules lacked the tinctorial properties of amyloid, but showed a strong immunostaining for keratin-like proteins. A systematic investigation of 12 APUDomas of bronchial or duodenopancreatic origin, using both light and electron microscopy, identified a few filamentous bodies in one case, a somatostatin cell tumour of ampulla of Vater. In both cases, the structures appeared similar to those previously reported in growth hormone cell pituitary adenomas as well as in a few bronchial or gut carcinoids. Whatever their nature, morphological data suggest that they are related to abnormalities in the secretory function, involving the Golgi apparatus, the endosecretory granules and the microtubular microfilamentous system.

Topics: Adult; Ampulla of Vater; Apudoma; Bronchial Neoplasms; Carcinoid Tumor; Common Bile Duct Neoplasms; Duodenal Neoplasms; Female; Humans; Immunoenzyme Techniques; Inclusion Bodies; Insulinoma; Keratins; Pancreatic Neoplasms; Protein Precursors