Antonio M. Mancini

Gelatinase A (mmp-2) and Its mrna Detected in Both Neoplastic and Stromal Cells of Tumors with Different Invasive and Metastatic Properties

Simultaneous presence of gelatinase A (MMP-2) and MMP-2 messenger RNA (mRNA) in 30 malignant tumors with various degrees of differentiation and biological behavior was evaluated by immunohistochemistry and in situ hybridization. The series consisted of 10 gastric carcinomas. 10 colorectal carcinomas, five squamous skin carcinomas, and five basal cell skin tumors. MMP-2 was detected in all cases. MMP-2 mRNA was expressed in the stromal cells in all cases and was more marked in the less-differentiated gastric and colonic carcinomas; it was also detected in the neoplastic cells of poorly differentiated tumors, particularly in those of the signet-ring cell type, both in the colon and stomach. The study confirmed that stromal cells have a specific role in tumor invasion and suggests a direct relationship between neoplastic epithelium and stromal cells in the most aggressive varieties.

Changes in the alveolar connective tissue of the ageing lung: an immunohistochemical study

The modifications of the extracellular matrix (ExM) components in the alveolar parenchyma of elderly subjects were investigated using a panel of polyclonal antibodies. The elastic fibers showed a notable decrease along the alveolar walls while type III collagen increased when compared with that of non-elderly controls. No variations of these components were detectable in the alveolar ducts or in the respiratory bronchioli. An increase in the thickness of the alveolar basement membranes was detected in some of the subjects when antibodies against type IV collagen and laminin were used, while antibodies to fibronectin and type V collagen did not reveal any modifications compared with the controls. The modifications revealed in the lungs of the elderly can be related to the alterations of the elastic recoil and pulmonary compliance observed in these subjects.

Sarcoidosis of the Peripheral Nerve: Clinical, Electrophysiological and Histological Study of Two Cases

Two cases of sarcoid polyneuropathy were diagnosed by histological examination of the nerve biopsy. The electrophysiological findings in both patients suggested a neuropathy of axonal type, confirmed by a morphological study of a sural nerve biopsy by light microscopy and on teased-fiber preparations. The sarcoid granulomas were multiple, especially in case 2; they were sparse in the epineurial and perineurial spaces and absent in the endoneurium, whose interstitial component contained cellular infiltrations of scattered macrophages. Blood vessel changes were a constant morphological feature. The mechanisms that possibly contribute to the pathogenesis of the sarcoid neuropathy are discussed in relation to previous reports.

Overexpression of p53 protein and Ki67 proliferative index in hepatocellular carcinoma: an immunohistochemical study on 109 Italian patients.

The overexpression of p53 protein and the Ki67 proliferative index was evaluated in 96 hepatocellular carcinomas (HCC), 67 in cirrhotic livers and 29 in non‐cirrhotic ones, and in 13 non‐carcinomatous lesions, all surgically resected from Italian patients. Overexpression of p53 was detected only in carcinomatous lesions, and was significantly related to the grade of HCC (P < 0.001). In fact, p53 was observed in 7/7 (100%) cases of grade IV, 13/43 (30.3%) of grade III, and 10/ 46 (21.7%) of grade II. The relationship between p53 and Ki67 scores was determined in serial sections from corresponding areas of both diffuse and patchy immunoreactivity. In the overall population, p53‐positive tumors showed a significantly higher Ki67 score (15.9 ± 5.5% vs 9.2 ± 4.3% [P < 0.001]). This observation was evident in all grades of HCC.

GASTRIC CARCINOIDS OF ECL CELLS

Clinical, histological, histochemical and ultrastructural characteristics of eight cases of carcinoid tumors of the non‐antral portion of the stomach are presented. Four cases with multiple polypoid lesions are accompanied by an increased level of gastrin. A normal level of gastrin was present in the other four cases with isolated tumor and a normal component of endocrine cells in the uninvolved mucosa. In the first group with multiple lesions, the histological and histochemical analysis of the endocrine cells revealed a wide range of appearances: a) “simple hyperplasia”, b) “nodular hyperplasia”, and c) carcinoid tumor. These aspects suggested a different pathogenesis for the carcinoid tumors of the non‐antral portion of the stomach with possible therapeutical implications. ACTA PATHOL. JPN. 35: 361–375, 1985.

Progressive Approach to the Cytologic Diagnosis of Retroperitoneal Spindle Cell Tumors

OBJECTIVE To assess the utility of fine needle aspiration biopsy (FNAB) in retroperitoneal spindle cell tumors with difficult tumor typing. STUDY DESIGN Thirty-six cases of spindle cell tumors of the retroperitoneum were studied. Cytological diagnoses were set progressively: first exclusively by morphologic criteria on routinely stained slides, and then with the aid of immunocytochemistry (ICC), electron microscopy (EM) and clinical data. RESULTS The morphologic diagnosis of benignity or malignancy was first made in double blind fashion by two researchers; it permitted an exact diagnosis in 31 cases (86%) by one examiner and 27 cases (75%) by the second. Using a progressive approach, benignity or malignancy was definitively determined in 35 cases (97%). As far as cytologic tumor typing is concerned, first it proved to be possible in 27 cases (75%) and then in 30 cases (83%) with the progressive approach. CONCLUSION FNAB proved to be a useful tool in the diagnosis of retroperitoneal spindle cell tumors. A progressive approach to cytopathologic diagnosis, correlating morphology with ICC and EM results and matching them with clinical data, permitted a better differential diagnosis between benign and malignant spindle cell tumors and increased the possibility of correct tumor typing.

Small liver masses in cirrhotic patients. A pathological clue for the morphogenesis of human hepatocellular carcinoma.

Eleven small primary liver lesions detected in four cirrhotic patients are reported in detail. Some lesions showed the histopathological features of macroregenerative nodules (MRN) containing foci of cellular and structural atypia or of hepatocellular carcinoma (HCC). Other lesions showed the histological abnormalities of the early developmental stage of HCC without a background of MRN. Finally one lesion is described with an equivocal background between benign and malignant, containing a focus of carcinoma. All lesions presented suggest the presence of different pathways in the morphogenesis of human HCC.

PRIMARY LIVER CELL CARCINOMA New Insight for a More Correct Approach to its Classification

Hepatocellular carcinomas, cholangiocellular carcinomas, and “indeterminate” forms have been studied by immunohistochemical detection of several antigens: a‐fetoprotein and CEA, as well as type IV collagen, laminin, and keratin. While the first two antigens were variably detectable in different samples, in the poorly differentiated areas of hepatocellular carcinoma type IV collagen and laminin were both absent. These basement membrane glycoproteins constantly surrounded the cholangiocellular carcinoma tubular structures and were always present in those areas of the “indeterminate” group where the cells were organized as pseudoglandular or ductular aggregates. Keratin was absent in all cases of hepatocellular carcinoma, was variably detectable in the “indeterminate” neoplasms and was always present in cholangiocellular tumors. The neoplasias with mixed histopathological features usually showed morphological and biochemical biliary differentiation at the periphery, in contact with the collagenous stroma. We postulate that in some cases hepatocarcinoma cells undergo metaplastic transformation giving rise to cholangiocellular forms. Type IV collagen, laminin, and keratin seem to be accurate markers of phenotypical differentiation and show that a continuous phenotypical spectrum exists between hepatocellular and cholangiocellular entities. ACTA PATHOL. JPN. 37:929–940, 1987.

Pericardial Multicystic Proliferation

&NA; We report the case of an intrapericardial lesion with the pathological features of a multilocular cyst, found on the adventitia of an aortic aneurysm in a 62‐yr‐old man. Microscopically, it consisted of numerous cavities lined by flattened or cuboidal cells with the immunocytochemical and electron microscopical features of mesothelium, sometimes forming a hyperplastic pattern. Numerous nerve bundles and collections of inflammatory cells were present in the stroma. These features were consistent with a reactive lesion.