Aldo Mombello

Peripheral giant cell granuloma: evidence for osteoclastic differentiation.

Nine cases of peripheral giant cell granuloma of the oral cavity have been immunohistochemically analyzed to assess the nature of the giant cells. Giant cells were unreactive when tested with antibodies recognizing myelomonocytic and macrophage markers (lysozyme, MAC 387, HAM 56) but showed strong immunoreactivity with MB1, an antibody reactive with osteoclasts. It is concluded that giant cells characterizing giant cell granuloma exhibit a phenotype distinct from other giant cells found in sites of chronic inflammation and may be true osteoclasts.

Neoplastic epithelial cells in a subset of human thymomas express the B cell-associated CD20 antigen.

A series of 36 human thymomas have been immunohistochemically analyzed using a panel of antibodies recognizing B-cell markers including CD20. Most thymomas exhibiting the cortical pattern, according to the criteria of Marino and Muller-Hermelink, were characterized by areas of medullary differentiation containing variable numbers of CD20+ B lymphocytes, thus mimicking the medulla of normal thymus. On the other hand, B cells were absent or rare in thymomas recognized as mixed using the same morphological criteria. Surprisingly, we observed in most mixed thymomas variable numbers of CD20+ spindle cells, characterized by long slender processes. Using double-marker analysis we could demonstrate the epithelial nature of these cells (expression of keratin and lack of lymphoid and B-cell-related markers). The immunoreactivity of thymoma epithelial cells with L26, an antibody widely used in the characterization of B-cell lymphomas, can represent a drawback of practical relevance in the differential diagnosis of mediastinal tumors.

Expression of transmembrane protein tyrosine phosphatase gamma (PTPgamma) in normal and neoplastic human tissues.

Aims:  To establish the conditions for protein tyrosine phosphatase gamma (PTPγ) detection in paraffin tissues using two antibodies raised against its NH2‐ (anti‐P4) and COOH‐termini (γTL1); to analyse its expression in normal tissues and to perform an initial screening of neoplastic tissues.

Quantitative Study of Ductal Breast Cancer Progression: Morphometric Evaluation of Phenotypical Changes Occurring in Benign and Preinvasive Epithelial Lesions

Fifty-nine cases of Breast Epithelial Proliferative Lesions (BEPL) and Ductal Carcinoma in Situ (DCIS), were studied by image analysis, to evaluate the nuclear changes occurring in the conventional diagnostic categories of ductal hyperplasia, atypical ductal hyperplasia and DCIS with quantitative methods. Diagnosis reproducibility is the main practical problem of these breast lesions. In fact, with subjective methods, the reproducibility appears to be very low and precarious especially for clinical demands. The objective, quantitative evaluation of cell phenotypical changes should be the method for both practical diagnostic problems and study of ductal cancer progression. The distribution pattern of the data in the feature, obtained with quantitative analysis, strongly suggests a continuum of changes, indicating an evolutionary process of Breast Ductal Carcinoma (BDC) progression in its preinvasive stage. Each observed case may be characterised by its own cellular, objective alterations and a progressive trend toward BDC can be stated. Since the actual changes of the proliferative phenotypes can be measured, and the values are reproducible, karyometric measurement may allow an objective grading of individual cases.

Quantitative Study of Breast Cancer Progression: Different Pathways for Various In Situ Cancers

The chromatin pattern in nuclei from breast ductal proliferative lesions was quantitatively evaluated with the objective of deriving measures of tumor progression. A total of 110 cases were analyzed. There were 38 cases of normal tissue or benign proliferative lesions, 41 cases of ductal carcinoma in situ (DCIS), and 31 cases of microinfiltrating DCIS and of infiltrating cancer. A total of 9424 nuclei were analyzed. High-resolution images were digitally recorded. For each nucleus, 93 karyometric features descriptive of the spatial and statistical distribution of the nuclear chromatin were computed. Data analysis included establishing a profile of relative deviations of each feature from “normal,” called the nuclear signature, and of lesion signatures as well as of trends of lesion progression. Two trends of evolution could be discerned: one from normal to hyperplasia, atypical hyperplasia, and comedo DCIS as representative of high-grade lesions; and the other from normal to hyperplasia to cribriform DCIS, solid DCIS, and infiltrating cancer, representing lower grade lesions. The nuclei in microinfiltrating foci are distinctly different from nuclei in high-grade comedo DCIS. The nuclei in microinfiltrating foci have a statistically significantly lower nuclear abnormality. They may represent outgrowing clones.

Quantitative Study of Ductal Breast Cancer Progression: A Progression Index (P.I.) for Premalignant Lesions and in situ Carcinoma

The diagnostic subjective assessment of ductal premalignant proliferative lesions and in situ carcinoma of the breast produces unsatisfactory results. Since the phenotypical cell changes in tumour progression toward infiltrating cancer constitute a continuum, a grading on a continuous scale of values produces a more reliable and reproducible characterization. The diagnostic assessment for any individual patient may be expressed by a progression index (P.I.): its numerical values are based on the cellular changes measured in the individual cases. In this study, the progression index is based on two morphometric features, nuclear size and nucleolar area. In addition, the method presented may produce a ratio, stating the relative likelihood that each case represents one of the conventional diagnostic categories. Such a likelihood ratio may be obtained from the bivariate distribution of nuclear size and nucleolar area for the conventional diagnostic categories.

Hypoplastic left heart syndrome with restrictive atrial septal defect and congenital pulmonary lymphangiectasis.

The presence of a restrictive atrial septal defect in hypoplastic left heart syndrome represents a surgical emergency and may negatively affect survival after operation. A neonate with such a disease association, requiring septectomy upon birth developed intractable respiratory failure due to congenital pulmonary lymphangiectasis. The therapeutic implications of this rare pathologic condition are discussed.

Quantitative study of ductal breast cancer--patient targeted prognosis: an exploration of case base reasoning.

Current analytic methodologies allow the extraction, even from small tumor masses, of extensive information on the biologic characteristics of malignant lesions, such as tumor aggressivity, metastatic potential, drug resistance, and host interactions. Clinical practice now offers a wide range of therapeutic strategies. Information technological advances offer the opportunity to refer to very large data bases of patient anamnestic data, response to treatment and clinical outcome. There is a need to formulate therapy and prognosis for each individual case. Case based reasoning is a knowledge based methodology where the outcome for complex situations can be predicted by referring to a large data base of cases of known outcomes. The preliminary data obtained from this study suggest that case based reasoning may offer a promising approach to individual targeted prognosis.

Immunohistochemical differentiation of follicular lymphoma from florid reactive follicular hyperplasia with monoclonal antibodies reactive on paraffin sections

In this study monoclonal antibodies which recognize lymphoid‐associated antigens on paraffin sections (LN1, MB2, L26, MT2, UCHL1) have been evaluated to assess their usefulness in the distinction between reactive and neoplastic lesions of lymphoid follicles. Thirty‐three follicular lymphoma samples and 36 reactive samples (lymph nodes and tonsils) were analyzed. MT2 appeared as the most valuable immunophenotypic marker as emerged from a comprehensive quantitative evaluation of 2329 reactive follicles and 2288 neoplastic follicles performed on MT2 immunostained sections. MT2‐positive follicles were found in all lymphoma samples but one. Overall 1908 of 2288 neoplastic follicles were judged as positive whereas no follicles with comparable strong MT2 immunoreactivity could be found in non neoplastic samples. These latter showed weak MT2 positivity only in about 10% (224/2329) of reactive follicles. This study confirms that MT2 follicular positivity can be considered a reliable marker of follicular neoplasia, although negative results ought to be considered with caution. The detection of centrofollicular cells outside the germinal centers, which is considered a reliable criterion of follicular neoplasia, was highly improved by LN1 immunostaining. On the other hand pan‐B antibodies such as L26 and MB2 were less informative because of the large number of B‐lymphocytes observed in interfollicular areas of nonneoplastic samples.

Immunohistochemical detection of arginine methylated proteins (MeRP) in archival tissues

Vezzalini M, Aletta J M, Beghelli S, Moratti E, Della Peruta M, Mafficini A, Mojica W D, Mombello A, Scarpa A & Sorio C
(2010) Histopathology57, 725–733 
Immunohistochemical detection of arginine methylated proteins (MeRP) in archival tissues