Galectin-3 is a presurgical marker of human thyroid carcinoma.

Galectin-3 is a carbohydrate-binding protein endowed with an affinity for beta-galactosides. It has been shown to play an important role in cell-cell and cell-matrix interactions and in pre-mRNA splicing. Furthermore, it is involved in the control of cell growth, neoplastic transformation, and metastasis. Interestingly, high levels of galectin-3 expression have been recently described in malignant thyroid neoplasias, but not in adenomas or in normal thyroid tissue. We investigated galectin-3 expression in human presurgical specimens obtained by fine-needle aspiration biopsy. We analyzed galectin-3 expression by immunoperoxidase staining in both paraffin-embedded cytological thyroid sediments (cell blocks) obtained by fine-needle aspiration biopsy and their histological counterparts. A total of 64 samples were examined: 17 follicular carcinomas; 18 papillary carcinomas; and 29 follicular adenomas. All cell blocks and histological samples of papillary carcinomas expressed high levels of galectin-3 at either the cytoplasmic or nuclear level. Among follicular carcinomas, all histological samples expressed galectin-3, whereas 14 of 17 corresponding cell blocks were positive in the cytoplasm. No evidence of cytoplasmic galectin-3 expression was observed in 26 of 29 follicular adenomas. Hence, cytoplasmic galectin-3 staining seems to be a reliable, easy, and cheap marker for presurgical diagnosis of follicular carcinomas and an even more suitable one for papillary carcinomas.

Galectin-3 as a presurgical immunocytodiagnostic marker of minimally invasive follicular thyroid carcinoma.

Thyroid nodules are a common occurrence in the general population, but only a small number of them are eventually diagnosed as cancers. Fine-needle aspiration biopsy (FNAB) is the most accurate and cost-effective method for the presurgical management of thyroid nodules, but it misses the differential diagnosis between thyroid follicular adenomas and follicular carcinomas. Among them, minimally invasive follicular carcinoma (MIC), also defined as encapsulated tumor, only differs from follicular adenoma for the exhibition of minimal, but entire thickness, infiltration of the capsule and/or vascular invasion. This feature cannot be assessed in FNAB and can occasionally be hard to recognize in surgical specimens. As reported in several studies, galectin-3 is a reliable marker of thyroid malignancy, but no data are available on MICs. We analyzed the immunohistochemical expression of galectin-3 in 17 MICs and 52 follicular adenomas in both preoperative paraffin-embedded cytological human thyroid sediments (cell blocks) obtained by FNAB and in the corresponding surgical specimens. Among the MICs, all surgical samples showed galectin-3 immunoreactivity in the cytoplasm, whereas 16 of 17 corresponding FNAB cell blocks were positive. No evidence of cytoplasmic galectin-3 expression was observed in 48 of 52 adenomas in both cell blocks and histological tissues. These findings indicate that galectin-3 is a reliable presurgical molecular marker of MIC, improving the accuracy of conventional FNAB. It also proves to be useful in the histopathological assessment of resected tumors having suspected malignant features.

Role of platelet activating factor in acute pancreatitis induced by lipopolysaccharides in rabbits.

In the present study we demonstrated that a single injection of endotoxin (lipopolysaccharides, E. Coli 0111-B4) into the superior pancreaticoduodenal artery of rabbits induced a dose-dependent acute necrotizing pancreatitis. The lesions observed by light microscopy were significant for 10 micrograms lipopolysaccharides and were maximal for 20 micrograms. After 24 h the main findings were edema, acinar cell vacuolisation, polymorphonuclear neutrophil infiltration and tissue necrosis. The pancreatic lesions developed strictly in the area supplied by the artery injected with lipopolysaccharides, without significant intestinal involvement. Since platelet-activating factor (1-O-hexadecyl-2-acetyl-sn-glycero-3- phosphocholine, PAF; 50-500 ng), a phospholipid mediator of endotoxin-induced inflammation and shock, was previously shown to cause an acute necrotizing pancreatitis in rabbits, the role of PAF in the development of acute pancreatitis induced by lipopolysaccharides was studied by evaluating: (1) the synergism between doses of lipopolysaccharides (5-10 micrograms), which produced a mild tissue injury, and doses of PAF (10 ng) not producing, per se, any significant injury, and (2) the effect of three structurally unrelated PAF receptor antagonists. The results obtained demonstrated that 10 ng of PAF significantly potentiated pancreatic tissue damage induced by 10 micrograms of lipopolysaccharides.(ABSTRACT TRUNCATED AT 250 WORDS)

[Primary sclerosing cholangitis associated with colonic Crohn disease and marked eosinophilia. Description of a case]. / Colangite sclerosante primitiva associata a morbo di Crohn del colon e spiccata eosinofilia. Descrizione di un caso.

We report a case of primary sclerosing cholangitis associated with Crohn disease of the large intestine and marked eosinophilia in a 64 year old woman. Clinical features, histologic findings at biopsy of the intestine and liver and the endoscopic retrograde cholangiopancreatography are described. The case report is discussed, particularly as regards treatment with biliary salts and aminosalicilic acid.

[Hemoperitoneum caused by cavernous angioma of the omentum]. / Emoperitoneo da angioma cavernoso dell'omento.

A case history is reported of a spontaneous, nontraumatic, hemoperitoneum in an eleven year old girl. The onset, the accompanying symptoms and the clinical course, mimicked those of acute appendicitis. However the etiology was found to be the spontaneous rupture of a cavernous hemangioma of the omentum. Only one other similar case has been reported in the literature.

Cold snare excision of small colorectal polyps.

This study describes a new technique for excision of small colorectal polyps in a series of 210 consecutive patients, who had total colonoscopy, and in whom any clotting problems had been excluded. A total of 288 small polyps of 5 mm or less in diameter were transected by mechanical strangulation with a polypectomy snare, but without applying any electrical energy. All polyps were recovered whole and sent for histologic examination. No case of perforation, serious bleeding, or mortality was recorded, nor was there any need for blood transfusion because of sudden or delayed bleeding. Of the small polyps, 56% were adenomas, 43% hyperplastic, and 1% were other types. No invasive cancer was found, but in seven small adenomas severe dysplasia was observed. No correlation between the macroscopic appearance of small polyps at endoscopy and their nature at histology was found. Our data confirm that all visible polypoid lesions of the colon should be removed, and that cold snare excision of small polyps is a safe and effective alternative method of treatment in patients without clotting problems.

Recurrent thromboembolism as a hallmark of Cushing's syndrome.

The present report describes a 54-year-old woman with a history of recurrent thromboembolic events. The clinical and physical examination led to suspect Cushing's syndrome. Screening tests (urinary free cortisol excretion and 1 mg dexamethasone) were inconclusive, but a detailed endocrine work up confirmed the presence of ACTH-dependent hypercortisolism. The patient was cured by the removal of a ACTH-secreting microadenoma by transsphenoidal route. The present case provides a clinical demonstration of a previous experimental evidence that a hypercoagulable state is present in Cushing's syndrome.

Asbestos body burden in decomposed human lungs.

The authors discuss the influence of postmortem tissue decomposition on the lung asbestos body (AB) burden, with the aim of evaluating the reliability of data obtained from autopsies performed for medicolegal purposes several months after deaths in possible connection with asbestos-related pathology. Eight autopsy cases were selected, each one with occupational exposure considered very probable on the basis of the history or pathologic findings. In each case the AB concentrations were assessed soon after death in one lung and after periods of 1 to 18 months in the others, which had been stored in sealed containers without fixation. AB concentrations consistently decreased with time in rotten lungs. The counts in some cases became negative a few months after death, even in cases with very high AB counts at first examination. It may be reasonably inferred that, in putrefied lungs from corpses exhumed after months of internment, the counts in digested tissues and the screening of histologic sections for AB may give false-negative results.

p27(kip1) immunoreactivity correlates with long-term survival in pleural malignant mesothelioma.

BACKGROUND: Pleural malignant mesothelioma (PMM) is a rare and highly aggressive tumor, whose development is strictly related to occupational exposure to asbestos. The prognosis of PMM is generally poor (median survival, 4-12 months), but a few have a relatively long survival. The objective of this study was to evaluate the use of the cell cycle-related proteins p27(kip1) and MIB-1 as prognostic indicators of survival in PMMs. METHODS: Of 621 PMMs, the authors selected 27 cases with a relatively long-term survival (> 24 months) and a control group of 36 PMMs having a shorter (usual) survival (< 24 months). RESULTS: The expression of the p27(kip1) was significantly higher in the long-term survival group compared with the control (short survival) group (81.41% vs. 31.94%; P < 0.0001). The PMMs of epithelioid histotype had a significantly higher p27(kip1) immunoreactivity compared with those of biphasic type (59.24% vs. 38.94%; P = 0.02). In agreement with the data in the literature, the proliferative activity (as detected by MIB-1 immunoreactivity) was significantly higher in short than long survival PMMs (43.53% vs. 14.11%; P < 0.0001) and in the biphasic histotype than in the epithelioid type (43.19% vs. 26.02%; P = 0.006). CONCLUSIONS: The combined expression of high/low p27(kip1) and low/high Ki-67 values identified with 100% specificity and sensitivity long versus short survivors. p27(kip1) represents a reliable additional predictive factor for PMMs and a useful marker to identify patients having a more favorable prognosis.

Epidermal growth factor receptor overexpression correlates with a poor prognosis in completely resected non-small-cell lung cancer.

BACKGROUND: We designed a prospective study to test epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC) in resected stage I-IIIA non-small-cell lung cancer (NSCLC) and to correlate overexpression with survival. PATIENTS AND METHODS: EGFR expression was evaluated in 130 consecutive NSCLC patients after radical surgery (60 squamous cell carcinomas, 48 adenocarcinomas, 22 large cell carcinomas: stage I, 41 (31%); stage II, 37 (29%) and stage IIIA, 52 (40%). RESULTS: Overall, 101 of 130 (78%) specimens expressed EGFR, and with a cut-off value of 10% positive cells 48 cases (37%) were classified as positive. At univariate analysis, EGFR was significantly more expressed in stage III (50%) than stage I (20%) and stage II (25%) (P <0.03). No correlation with histotype was found. After a median follow-up of 84 months, both median survival time (18 versus 50 months), 2-year (43% versus 70%) and 5-year (31% versus 46%) survival rates of positive cases were significantly lower than negative ones [P <0.001; hazard ratio 1.96; 95% confidence interval (CI) 1.16-3.30]. At the multivariate analysis, EGFR overexpression and stage emerged as independent factors for cancer-related mortality. CONCLUSION: In patients with radically resected stage I-IIIA NSCLC, EGFR overexpression predicts shorter survival, thus representing a valuable prognostic factor.

Different immunohistochemical patterns of TGF-beta1 expression in benign and malignant adrenocortical tumours.

OBJECTIVE: Transforming growth-factor beta1 (TGF-beta1) influences a number of specific functions of adrenocortical cells in several animal species. The aim of our study was to evaluate by immunohistochemical analysis the presence and distribution of TGF-beta1 in normal adrenal tissue and in different adrenal tumours. PATIENTS: We analysed 8 functioning (5 adenomas and 3 carcinomas) and 15 non functioning (6 adenomas and 9 carcinomas) adrenal tumours and 6 normal adrenal glands. RESULTS: In normal adrenal glands, the glomerulosa and the reticularis zones displayed diffuse cytoplasmic staining, while the fasciculata zone was almost completely negative. Functioning adenomas displayed cytoplasmic staining restricted to compact cells while in nonfunctioning adenomas, prevalently composed by clear cells, no staining was observed. Overall, adrenal carcinomas were characterized by the lack of cytoplasmic positivity and by sporadic positive cells around vessels both in functioning and in nonfunctioning tumours. CONCLUSIONS: TGF-beta1 expression is associated with active steroid secretion in normal adrenal tissue, as well as in benign cortical adenomas, while this relationship is lost in primary adrenal malignancies. These data provide indirect evidence for a regulatory role played by TGF-beta1 on steroid secretory pathways.

RET proto-oncogene mutation in a mixed medullary-follicular thyroid carcinoma.

A case of a patient with an uncommon thyroid carcinoma, showing histological and immunohistochemical features of both follicular and parafollicular cells is described. Somatic point mutation (ATG to ACG heterozygotic mutation at codon 918) of the RET proto-oncogene was detected in tumor tissue, as confirmed by immunohistochemical expression of RET oncoprotein. Our findings suggest that constitutive RET proto-oncogene activation may be involved in the development of mixed medullary-follicular thyroid carcinoma.

Immunohistochemical assessment of Ki-67 in the differential diagnosis of adrenocortical tumors.

OBJECTIVES: To evaluate the utility of Ki-67 immunohistochemical analysis in the differential diagnosis between benign and malignant adrenocortical neoplasms. METHODS: Tissue specimens were obtained from 37 patients referred to our institute from 1990 to 1999. The indications for adrenalectomy were adrenal-dependent Cushing syndrome (n = 9), hyperandrogenism (n = 1), mineralocorticoid excess (n = 8), and nonfunctioning adrenal masses (n = 19). The histologic diagnosis was cortical adenoma in 26 of 37 patients and cortical carcinoma in the remainder. Normal adrenal glands were obtained from subjects who underwent radical nephrectomy because of initial renal carcinoma. Immunohistochemical analysis was performed using the monoclonal antibody anti-Ki-67 (clone MIB-1). The Ki-67 labeling index was expressed as the number of positive cells per 1000 cells.Results. The average Ki-67 expression was 2.0 per thousand +/- 1.2 per thousand (SD) in normal adrenal glands, 11.3 per thousand +/- 16.0 per thousand in adenomas, and 185.8 per thousand +/- 60.3 per thousand in carcinomas (P <0.0001). A threshold value of the Ki-67 labeling index between 70 per thousand and 90 per thousand reliably separated adenoma from carcinoma. A significant inverse correlation was found between Ki-67 expression and overall survival in patients with adrenal carcinoma (r = -0.74, P = 0.009). CONCLUSIONS: Immunohistochemical assessment of the nuclear antigen Ki-67 can be useful in the differential diagnosis between adrenocortical adenoma and carcinoma. High levels of Ki-67 seem to indicate patients with adrenocortical cancer with a worse prognosis.

Molecular heterogeneity of B-lineage diffuse large cell lymphoma.

B-lineage diffuse large cell lymphoma (B-DLCL) arising de novo is characterized by a marked degree of clinical heterogeneity. To determine whether or not the clinical heterogeneity of de novo B-DLCL is reflected by heterogeneity in the molecular features of these tumors, we investigated the pattern of distribution of several genetic lesions in 70 cases of de novo B-DLCL at diagnosis. The panel of genetic lesions tested comprised the molecular alterations most frequently detected in B-DLCL, including rearrangements of BCL2, BCL6, and MYC as well as deletions of 6q and mutations of TP53. One or more genetic lesions were detected in 39/70 cases of B-DLCL. Isolated structural alterations of BCL2, BCL6, 6q or TPS3 were detected in 8/70, 10/70, 11/70, and 3/70 cases, respectively. No isolated MYC lesions were detected. Six cases carried different combinations of two genetic lesions, including lesions of BCL2 + BCL6 (1 case), BCL2 + MYC (1 case), BCL2 + 6q (2 cases), or BCL6 + 6q (2 cases). One case had accumulated three genetic lesions, namely a rearrangement of BCL2 and BCL6 and a mutation of TPS3. Overall, these data show that multiple distinct patterns of genetic lesions may associate with de novo B-DLCL, indicating that the molecular pathogenesis of this group of lymphomas is characterized by a high degree of molecular heterogeneity.