The Veneto Region's Barrett's Oesophagus Registry: aims, methods, preliminary results.

BACKGROUND: The natural history of Barrett's Oeosphagus is not completely clarified and Barrett's Oeosphagus Registries are considered useful tools to expand our knowledge on this disease. A Barrett's Oeosphagus Registry has been therefore established in the Veneto Region and neighbouring provinces. AIMS: The aims of the Registry are to assess the demographical, endoscopical and histological characteristics of Barrett's Oeosphagus patients; the prevalence of non-invasive neoplasia and Barrett's Adenocarcinoma and the timing and incidence of Barrett's Oeosphagus progression to malignancy. METHODS: An interdisciplinary committee of endoscopists, pathologists and information technology experts was established in 2004 to design a website-based Barrett's Oesophagus Registry for the Veneto Region and neighbouring north-eastern Italian provinces. Protocols for endoscopies and biopsies and standard reports were carefully defined. RESULTS: In the first 18 months, 397 patients with endoscopically visible and histologically proven Barrett's Oeosphagus were enrolled in the Registry; the median age of these patients was 66 years (male:female=3:1). Most patients (75%) had a Short Segment of Barrett's Oesophagus (3 cm). Long Segment of Barrett's Oesophagus patients were 5 years older than the Short Segment of Barrett's Oesophagus patients (p<0.05), suggesting a progression from Short Segment of Barrett's Oesophagus to Long Segment of Barrett's Oesophagus. Though no data are available on the incidence of non-invasive neoplasia or Barrett's Adenocarcinoma (i.e., progression to cancer at least 12 months after enrolment), the prevalence of neoplastic lesions (found within 12 months of enrolment) was 5% for Short Segment of Barrett's Oesophagus and 19% for Long Segment of Barrett's Oesophagus, indicating that a careful multiple-biopsy endoscopic protocol is needed, especially when Long Segment of Barrett's Oesophagus are suspected at endoscopy. The prevalence of Barrett's Adenocarcinoma among patients with non-invasive neoplasia was 1/17 cases of low-grade non-invasive neoplasia and 2/3 cases of high-grade non-invasive neoplasia, indicating that these patients require strict endoscopic and bioptic follow-up. CONCLUSION: A regional Barrett's Oeosphagus Registry is feasible at a relatively low cost and enables significant data to be collected in a relatively short time. The use of a standardised endoscopic nomenclature and report form, a strict biopsy protocol, a standard report for pathologists improves the quality of endoscopic and histological diagnoses.

Classification tool for the systematic histological assessment of hepatocellular carcinoma, macroregenerative nodules, and dysplastic nodules in cirrhotic liver.

AIM: To design a classification tool for the histological assessment of hepatocellular carcinoma (HCC), dysplastic nodules (DN), and macroregenerative nodules (MRN) in cirrhotic liver. METHODS: Two hundred and twelve hepatocellular nodules (106 HCC; 74 MRN; 32 DN) were assessed systematically, quantitatively, and semiquantitatively as appropriate for 10 histological features that have been described as helpful in distinguishing small HCC, DN, and MRN in cirrhotic livers. The data were analyzed by multiple correspondence analysis (MCA). RESULTS: MCA distributed HCC, DN, and MRN as defined by traditional histological evaluation as well as the individual histological variables, in a "malignancy scale". Based on the MCA data representation, we created a classification tool, which categorizes an individual nodular lesion as MRN, DN, or HCC based on the balance of all histological features (i.e., vascular invasion, capsular invasion, tumor necrosis, tumor heterogeneity, reticulin loss, capillarization of sinusoids, trabecular thickness, nuclear atypia, and mitotic activity). The classification tool classified most (83%) of a validation set of 47 nodules in the same way as the routine histological assessment. No discrepancies were present for DN and MRN between the routine histological assignment and the classification tool. Of 25 HCC assigned by routine assessment in the validation set, 8 were assigned to the DN category by the classification tool. CONCLUSION: We have designed a classification tool for the histological assessment of HCC and its putative precursors in cirrhotic liver. Application of this tool systematically records histological features of diagnostic importance in the evaluation of small HCC.

Detection of nodal micrometastases using immunohistochemistry and PCR in melanoma of the arm and trunk.

Sentinel node (SN) mapping and biopsy seems at present the best way to assess the nodal status in cutaneous melanoma without removing the lymphatic chain. The procedure is minimally invasive, safe and low cost, and allows selection of patients who can benefit from elective node dissection. From March 1997 up to July 1999 we examined 112 SNs excised after lymphatic mapping from 95 patients (48 males and 47 females) with stage I cutaneous melanoma affecting the trunk or limbs. Of these, 88 SNs from 74 patients were submitted to polymerase chain reaction (PCR) in order to detect tyrosinase mRNA. A new antibody (anti-tyrosinase, Clone T311, IgG2a type, Lab Vision Corporation) was used to detect nodal micrometastases. The search for micrometastases was histologically positive in 15 SNs and negative in 97. The 88 SNs examined using molecular biology were positive in 40 cases and negative in 48. In 28 only the PCR was positive. The new antibody used to detect micrometastases was shown to be very useful. Cases positive on both conventional histology and PCR were Clark level II or more and were thicker than 0.6 mm. No difference with regard to site or sex was observed. Lymphoedema and hypersensitivity reactions, nor the inability to work, did not occur. Only patients with histologically proven micrometastases underwent elective node dissection. Cases positive only on molecular biology were submitted to close follow-up.

p21 expression in colorectal carcinomas: a study on 103 cases with analysis of p53 gene mutation/expression and clinic-pathological correlations.

The WAF1/CIP1 gene product, p21, an inhibitor of cyclin-dependent kinases, is a critical downstream effector in the p53 pathway. The expression of p21 in human neoplasms is heterogeneous, and may be related to p53 functional status. We evaluated p21 immunoreactivity in 103 colorectal carcinomas (CC) in relation to the p53 gene and protein alterations and clinico-pathologic parameters. High p21 expression (more than 10% reactive cells) was seen in 39% of cases. p21 staining was heterogeneous and often detected in clusters of tumour cells; in some tumours p21 staining was more pronounced in superficial areas. No relation was seen between p21 immunoreactivity and site of the tumours (right vs left), TNM stage and grade. p21 expression was related to p53 status as evaluated with IHC or with SSCP analyses, low p21 expression usually being associated with p53 protein overexpression (P=0.048) and p53 gene alteration (P=0.005). The strongest associations were seen when the combined p53/p21 immunophenotype was compared with p53 gene alterations (P=0.0002). These data support the hypothesis that p21 expression in CC is mainly related to p53 functional status, suggesting that p21 expression could be an interesting adjunct in the evaluation of the functional status of the p53 pathway in CC.

Fine needle aspiration of myofibroblastoma of the breast. Case report.

The cytologic and histologic findings of myofibroblastoma of a man's breast are reported. Cytologic specimens showed many scarcely cohesive clusters of bipolar or stellate cells. The cytoplasm was moderately eosinophilic and had clearly-defined edges. The nucleus was characterized by round or coffee-bean shape, regular chromatin and small nucleolus. Atypical features were absent. Immunocytochemical tests confirmed the mesenchymal nature of the lesion showing negativity for CAM 5.2 and positivity for vimentin. We stress the value of fine-needle aspiration biopsy in association with clinical- examination, mammography and/or echography in establishing the preoperative diagnosis of this benign tumor.

[A giant-cell tumor of the mandibular condyle. A report of a clinical case]. / Tumore a cellule giganti del condilo mandibolare. Presentazione di un caso clinico.

The authors present a case of a giant cell tumor of the mandibular condyle, which is a very rare condition. Problems relating to diagnosis and treatment are examined. Specifically non neoplastic and neoplastic lesions in which giant cells are identified have been evaluated.

Quantitative growth fraction evaluation with MIB1 and Ki67 antibodies in breast carcinomas.

Ki67 and MIB1 monoclonal antibodies are directed against different epitopes of the same proliferation-related antigen. Whereas Ki67 works only on frozen sections, MIB1 may be used also on fixed sections. The authors immunostained a series of 40 breast carcinomas with MIB1 and Ki67 antibodies on serial frozen sections and on fixed material. The Ki67 labeling index (LI) was 12.9 +/- 8.9 and 12 (mean +/- SD and median, respectively). MIB1 LI was 21.2 +/- 11.9 and 19.5 on frozen sections and 24 +/- 15.2 and 21.5 on fixed sections (mean +/- SD and median, respectively). Ki67 LI and MIB1 LI on frozen and fixed sections were strictly correlated (P < .001). The results are in keeping with the reported coincidental nuclear staining pattern of Ki67 and MIB1, but the mean and median values of MIB1 LI are almost twice the values of Ki67 LI. The cut-off values to define high and low proliferative activity with the two antibodies are therefore different. The differences in immunolabeling may be due to better survival of the MIB1 epitope in freezing and acetone fixation or to differing accessibilities of the MIB1 and Ki67 epitopes during the cell cycle due to molecular conformational modifications. The MIB1 monoclonal antibody is a reasonable substitute for the Ki67 monoclonal antibody. The advantages of MIB1 immunostaining on paraffin sections include the feasibility of retrospective studies and of obtaining clear morphologic specimens that are optimal for use with computer-assisted image analysis systems. Our image-processing system allows automatic nuclear counting, detects positive nuclei and measures their staining intensity.

Fibrinogen inclusions in liver cells: a new type of ground-glass hepatocyte. Immune light and electron microscopic characterization.

A new type of ground-glass hepatocyte is described. The appearance is due to pale, homogeneous, weakly eosinophilic inclusions filling a portion of or the entire hepatocytic cytoplasm. On haematoyxlin and eosin stained sections, these cells closely resemble ground-glass hepatocytes described in other conditions. However, they are negative on special stains for HBsAg and on PAS staining. Immunohistochemically, they reveal a selective and exclusive positivity for fibrinogen. On electron microscopy, the immunoreactive fibrinogen appears as amorphous, fluffy or granular material within dilated cisternae of the rough endoplasmic reticulum. This finding suggests intracellular storage possibly reflecting a defective intracellular transport of fibrinogen.

[Acute herpes simplex hepatitis with favorable outcome in an otherwise healthy adult]. / Epatite acuta da Virus Herpes Simplex a decorso favorevole in un adulto normale.

A non fatal case of Human Herpes Simplex hepatitis is presented, and the features of 15 previously reported cases are briefly reviewed. The patient, an otherwise normal middle-aged woman, presented as acutely ill, with typical mucocutaneous lesions, but recovered in a few days. Liver biopsy showed multiple focal areas of cellular necrosis with marked inflammatory infiltration, but without evidence of intranuclear eosinophilic inclusions. The possible underestimation of cases of Herpes Simplex hepatitis is proposed.

Primary malignant mixed mesodermal tumor of the gallbladder. Report of a case and critical review of diagnostic criteria.

A rare case of primary malignant mixed mesodermal tumor of the gallbladder arising in a 75 year old woman is reported. The previously published cases of similar tumors were reviewed in order to outline the histological features and the histogenesis. In diagnosing a malignant mixed mesodermal tumor of the gallbladder it was imperative that we excluded malignant neoplasms with multiple histological patterns. The diffuse and close intermingling of the epithelial and mesenchymal component ruled out a collision tumor. The high mitotic rate, the typical reticulin pattern and the obviously malignant osteoblasts excluded a spindle cell carcinoma with osseous metaplasia. The authors conclude that this is the first case of malignant mixed mesodermal tumor with evident osteosarcomatous areas, described in the gallbladder.

Human islet cell tumor storing pancreatic polypeptide: a light and electron microscopic study.

A 45-year-old man was operated for surgical treatment of a long-standing peptic ulcer disease and upon inspection of the pancreas for suspected Zollinger-Ellison syndrome, tumor nodules were found in this organ. The tumor tissue examined by immunofluorescence showed specific staining only after incubation with anti-pancreatic polypeptide. Negative results were obtained with antisera directed against insulin, pancreatic glucagon, somatostatin, GLI, VIP, secretin, and gastrin. Examination of the tissue by electron microscopy revealed a homogeneous population of small granule-containing cells. This case, therefore, illustrates a tumor composed of one single hormone-producing cell type and allows definition of the ultrastructural features of human pancreatic polypeptide-containing cells.

Endocrine tumor of the pancreas composed of argyrophil and B cells. A correlated light, immunofluorescent, and ultrastructural study.

A correlated morphological study, employing endocrine cell stains, immunofluorescence, and electron microscopy, was performed on biopsy specimens taken from a pancreatic tumor and liver metastases in a woman with hypoglycemic symptoms and high fasting insulin levels. The study revealed the tumor to be composed of two different endocrine cell populations, irrespective of the primary or metastatic growth. The first cell type fulfilled all the morphological characteristics of the islet B cells. The second was argyrophil (with the Grimelius silver method) and showed the morphological pattern of polypeptide-hormone-producing cells. With the lack of a detectable symptomatology, normal blood levels of the hormones other than insulin, and the negative results of a large number of immunofluorescence tests, we were unable to indetify the specific nature of the second type of cells.