C3a, TNF-alpha and interleukin myocardial expression in a case of fatal sudden cardiac failure during clinic reactivation of systemic lupus erythematosus.

Isolated myocarditis, or dilated cardiomyopathy, is a rare and usually late clinical manifestation of systemic lupus erythematosus (SLE). Increased levels of complement split products are associated with disease activity. Injury of the vascular endothelium due to complement activation and immune complexes may contribute to the vasculopathy in SLE. We present a case of sudden cardiac failure and death in a 28-year-old Caucasian man, during reactivation of SLE. To explain the sudden cardiac failure, we looked for anti-tumour necrosis factor (TNF)- proportional, variant and anti-interleukin (IL) expression in cardiac cells, and anti-complement (anti-C)3a in small cardiac vessels. The immunohistochemical examination of heart specimens revealed a strong positive reaction in cardiac myocytes for antibodies anti-TNF- proportional, variant and IL-8, and a milder positive reaction for antibodies anti-IL-15 and IL-10. A strong positive reaction of C3a in small cardiac vessels was observed in all specimens. Furthermore, the expression of CD4 and CD8 showed a strong positive reaction in pericardium and valvular endocardium, and a lesser positivity in myocardial specimens. TNF appears to have played a major proinflammatory role in this fatal case.

The quality of life in Italian psoriatic patients treated with biological drugs.

AIM: Psoriasis is well known to affect negatively daily activities, occupational and sexual functioning. We investigated whether the improvement of skin lesions obtained with the new biological drugs comes with by a better Quality of Life (QoL) as well. METHODS: Thirty patients with moderate to severe psoriasis treated with either anti-CD11 (13) or anti-TNF-α molecules (17) were studied. The severity of skin lesions was evaluated, before the biological therapy (T0) and after 6 months of treatment (T1), by the Psoriasis Area and Severity Index (PASI) and the Body Surface Area (BSA). QoL was evaluated by the Dermatology Life Quality Index (DLQI) and by the Psoriasis Quality of Life (PsoriQoL). RESULTS: DLQI and PsoriQoL mean scores shifted significantly from 16.5 to 2 respectively. At T0, PASI did not correlate significantly with DLQI. DLQI nor PsoriQoL correlated significantly with age and with the duration of the disease. PASI correlated significantly with DLQI of patients with arthropathy only, but did not with DLQI of patients without arthropathy. At T1, PASI was not correlated significantly with DLQI nor with PsoriQoL. CONCLUSION: The patient affected by psoriasis suffer an impairment of their QoL which seems to be independent from many obvious factors, such as age, duration of the disease and, mainly, its severity. QoL does not seem to be influenced significantly by arthropathy. Other factors, of both genetic or environmental nature, could play a determinant role in depriving psoriatics of a good QoL.

Comparative genomic hybridisation in malignant deciduoid mesothelioma.

BACKGROUND: Malignant deciduoid mesothelioma is a rare variant of epithelioid mesothelioma. This tumour generally has poor prognosis, and can be asbestos related. AIM: To identify peculiar genetic changes responsible for critical phases in pathogenesis of malignant deciduoid mesothelioma and their prognostic relevance. METHODS: Comparative genomic hybridisation was carried out in six cases of malignant pleural deciduoid mesothelioma, four sporadic and two familial. All cases were found to be asbestos related. Four patients died during follow-up and the mean survival was 29.5 (SD 14.2, range 12-43) months. RESULTS: Genetic abnormalities were found in all the tumour tissues, the most frequent being chromosomal gains at 1p, 12q, 17, 8q, 19 and 20 and losses at 13q, 6q and 9p. Survival was found to be longer in those patients who presented a smaller number of losses (< or =2) in the tumorous chromosomes. CONCLUSIONS: Although numerous genetic changes are presented by deciduoid mesotheliomas, certain chromosomal regions are preferentially affected. The clinical outcome for this mesothelioma subtype is predicted by the number of losses.

p53 protein expression in central nervous system neoplasms.

AIMS: To demonstrate, immunohistochemically, p53 protein expression in a selection of central nervous system tumours; to investigate the relation between p53 expression and that of the proliferation related antigen, PCNA. METHODS: Surgical specimens from 86 central nervous system tumours were routinely fixed, paraffin wax embedded, and immunostained with a monoclonal (PAb 1801) and a policlonal antibody (CM1) p53 protein and a monoclonal antibody against PCNA (PC10). Normal brain samples obtained at necropsy and 10 surgically obtained samples of gliotic brain parenchyma were also immunostained. RESULTS: p53 protein expression was observed in 35 of 86 brain tumours, suggesting frequent p53 gene mutation. p53 protein alterations were associated with all grades of malignancy in tumours displaying solely astrocytic differentiation, with the exception of pilocytic astrocytomas. In those showing oligodendroglial or ependymal differentiation they appeared to be restricted almost to only high grade lesions. No p53 immunoreactivity was observed in normal or gliotic brain tissue; p53 altered expression was not related to the percentage of PCNA labelled cells. CONCLUSIONS: The use of sophisticated gene amplification techniques or highly sensitive immunohistochemical methods might be useful in distinguishing between reactive and neoplastic astrocytic lesions, and in the identification of malignant progression in other non-astrocytic glial tumours. Tumours with very similar histogenetic differentiation features might actually be a genetically heterogeneous group with possible different clinical courses.

Primary intraosseous carcinoma of the mandible: a case report.

A case of primary intraosseous carcinoma of the mandible in a 75-year-old man is reported. This tumor is an uncommon lesion arising from odontogenic rests. This tumor affects men more than women and is more frequent in the sixth and seventh decades of age. Most tumors occur in the posterior mandible as painful, non-ulcerated lesions, even if several cases have shown complete absence of subjective symptoms in early phases; often they are detected first on routine radiographs. Radiographically the lesion usually shows a fully enclosed, irregular pattern of bone destruction, even if sometimes the margins are well defined. The accepted treatment is radical surgery; but metastases could occur in lymph nodes.

Non-Hodgkin's lymphoma diagnosis aided by the S.A.M. system.

In the attempt to discriminate between centroblasts and immunoblasts, an analytical morphometrical procedure was adopted, considering the nuclei of a randomly selected centroblastic and immunoblastic population from non-Hodgkin's lymphomas and the nucleoli of a more restricted number of the same neoplastic population. All the size-independent shape-descriptor parameters extracted for each step of the mathematical analyses used were submitted to Hotelling's multivariate discriminant analysis that enabled us to achieve a good distinction (3% error) between centroblasts and immunoblasts when nuclear and nucleolar parameters were used together.

Differential diagnosis between thyroid follicular adenoma and carcinoma. Analytic morphometric approach.

In this study some nuclear dimensional and analytical parameters were evaluated in order to distinguish follicular atypical adenoma from follicular carcinoma of the thyroid. Eighty nuclei from carcinomas, 80 from adenomas and 80 from normal thyroid were studied. Analytical parameters obtained by the nuclear shape study (by S.A.M. system) as well as dimensional parameters were submitted to univariate statistical analysis. On the ground of our results atypical adenoma could be considered as an intermediate aspect of a progressive change from benign to malignant even if they are closer to normal thyroid than to carcinoma.

Hand-mirror (HM) cells in acute lymphoblastic leukaemia (A.L.L.). An attempt at cellular classification by morphometric analytical parameters using the S.A.M. (Shape Analytical Morphometry) system.

A morphometric study of the nuclear and cytoplasmic shape of a blastic population in a case of HM-A.L.L. was performed by comparing the two differently shaped populations with and without HM configuration. The results obtained using analytical size-independent parameters created by the S.A.M. work-station enable us to characterize the shape of both blastic cell populations quantitatively, and strongly suggest the existence of shape modulation from one cellular type toward the other. Thus a possible sequence from blastic cells (having regular, rather round nuclei) to HM cells (characterized by high distortion of both nucleus and cytoplasm) was proposed.

Morphometrical investigation of medulloblastoma nuclei by S.A.M. (Shape Analytical Morphometry) software system.

In order to characterize medulloblastomas and to get over the difficulties sometimes encountered in differential diagnosis, a double morphometric procedure has been applied to its nuclei. The first consisted of size measurements (maximum diameter, area and perimeter), the latter is represented by S.A.M. (Shape Analytical Morphometry) software-system specifically implemented to describe shape of biological structure by analytical parameters. Analytical and dimensional parameters submitted to Hotelling's multivariate discriminant analysis gave the best results when used together in convenient discriminant subsets, thereby allowing a good distinction between medulloblastoma in comparison with neuroblastoma, Ewing's tumor, lymphoblastic and lymphocytic lymphoma. These results underline the usefulness of morphometric characterization also for practical diagnostic purposes.

Pure ductal carcinoma in situ and in situ component of ductal invasive carcinoma of the breast. A preliminary morphometric study.

Nuclear pleomorphism is a fundamental feature in evaluating the aggressiveness of ductal carcinoma in situ (DCIS) of the breast. In this study, pure DCIS and the in situ component (IS-comp) of invasive duct carcinoma (IDC) are compared in order to verify if these are two different entities or the same process observed at different times during its evolution. Five cases of pure DCIS and nine of IDC with extensive in situ component were selected. They were moderately and poorly differentiated. 30 nuclei for each DCIS, and 30 nuclei for both the in situ and invasive component of each IDC were studied; thus, a total of 720 nuclei were submitted to the SAM (Shape Analytical Morphometry) analysis, which enables a numerical expression not only of dimensions (area, perimeter, diameter) but also of nuclear contour irregularities and nuclear shape distortions. Univariate statistical comparisons were carried out between the nuclei of: (1) DCIS and in situ component of invasive duct carcinoma, (2) DCIS and the invasive component of infiltrating carcinoma and (3) between the in situ and invasive component of infiltrating carcinoma. Multivariate analysis was utilized to compare nuclei of DCIS with the in situ component of IDC. The in situ features of each tumor were also evaluated with the mitotic index (MI). Nuclei of pure DCIS resulted significantly larger (p < 0.001) and with a more regular shape (p < 0.001) than those of the in situ component of IDC. No differences were observed between the nuclei of the in situ and the invasive component of infiltrating carcinomas. Multivariate statistical analysis discriminated 77% of nuclei of in situ proliferation when both G2 and G3 tumors were considered, and 80% when only G3 tumors were considered. In conclusions morphological differences exist between pure DCIS and the in situ component of IDC, which may be an expression of their biological behavior; moreover, these morphological differences seem to have a better discriminating power within the same histological grade.

Quantitative morphometrical investigation of basal cell layer in laryngeal premalignant lesions.

Histological diagnosis of laryngeal dysplasia is quite subjective. Since morphometry is highly reproducible, this method was applied to compare shape and size variations of the basal nuclei of the laryngeal epithelium in normal, laryngeal intraepithelium neoplasia (LIN) and invasive carcinoma to assess the reliability of light microscopic criteria used in grading dysplasia according to Friedman classification. Morphometrical analysis was carried out by Shape Analytical Morphometry (S.A.M) system. The logical architecture assumes that each irregular shape contains elements of two distinct logical domains: gross distortions that interest the contour and its local perturbations. These features were investigated separately by analytical procedures to acquire independent parameters both on the logical level and the numerical one. The nuclear area significantly increased from normal to carcinoma (p<.001). The increasing of the nuclear area was evident also in LIN I. Nuclear distortions were present in LIN II and LIN III. The highest nuclear contour irregularities were found in LIN III. Multivariate analysis showed a difficulty in discriminating various grades of dysplasia, especially between LIN I and LIN II (31% of error). In conclusion, our results indicate that nuclear pleomorphism of the basal cells layer, using a unique evaluator, is an unsatisfying criterion to distinguish moderate dysplasia.

Nuclear shape and axillary metastases in breast cancer. Analytic morphometry of aspiration smears.

The aim of this work was to seek quantitative parameters other than dimensions to describe nuclear shape and, by this means, to determine the sum of contour irregularities and large asymmetries and seek a connection with the biologic behavior of the tumor. Nuclei of the cells obtained from 57 aspiration smears of breast cancers were studied. Dimensional parameters (area, perimeter, maximum diameter and roundness factor) and analytic parameters were computed by the Shape Analytical Morphometry software system to evaluate both contour irregularities and asymmetry of nuclear shape. All the tumors were subdivided according to their diameters into two groups: T1 tumors, the maximum diameter of which was < 2 cm (18 cases), and T2 tumors, the maximum diameter of which was > 2 cm and < 5 cm (39 cases). Among T1 tumors, both dimensional and analytic parameters were highly significant (P < .001) in distinguishing tumors with (N+) and tumors without (N-) axillary metastases, while among larger tumors (T2) only the analytic parameters showed degrees of significance, albeit variable. It could be inferred that in smaller tumors, aggressiveness is related to an increase in nuclear dimensions and shape distortions more so than in larger tumors.

[Mixed carcinoid-adenocarcinoma tumor of the appendix: a case report and diagnostic and therapeutic considerations]. / Tumore misto carcinoide-adenocarcinoma dell'appendice: caso clinico e considerazioni diagnostico-terapeutiche.

The layout of the work has stayed motivated from the recent observation of mixed carcinoid, located to the appendix and wide to the peritoneal cable, joint to our observation in an elderly patient with aspecific demonstration clinical-symptomatologic. The study of the endocrine tumors is in continuous evolution also if, to the actual state, there is a better comprehension of this neoplasm, variegated and complex and, under some appearances, still not known well. Jejunoileal carcinoid tumors differ, under many appearances, from those occurring in other sites of the gut. They have relatively high rate of transmural invasion and aggressive clinical behavior, contrasted by a scarce objectivity; the demonstration of symptoms generally implicates the presence of an illness in advanced stage. Also pharmacological therapy made important progress, with the possibility of administer composed able to interfere with the development and the neoplastic growth.

Gastro-intestinal stromal tumor (GIST): case report.

Gastro-intestinal stromal tumors (GISTs), as currently defined, represent the largest category of primary non epithelial neoplasms of the gastrointestinal tract. They arise from mesenchymal cells located in the wall of the organ and show a remarkable variability in their differentiation pathways. For this reason there is relevant degree of confusion in their interpretation. On the basis of immunohistochemical and ultrastructural studies these neoplasms are divided into several categories: leiomyomas, schwannomas and less differentiated tumors referred as GIST. In the small bowel GIST are uncommon. Usually asymptomatic, they could be the cause of surgical emergencies like massive bleeding, obstruction, intussusception or perforation. Generally benign, an higher percentage of malignant cases are described in the small bowel. The Authors report a case of malignant GIST of the small intestine presented with bowel obstruction by ileal invagination. In this case, as usually it happens in malignant GIST, the final diagnosis was obtained by an abdominal surgical exploration.

Is adipose tissue a normal component of the myocardium?

We performed a histological comparative study between endomyocardial biopsies taken from 138 patients with various cardiac pathologies and from 42 autoptic hearts (all negative for right ventricular dysplasia), measuring the amount of adipose tissue in isolation or associated with fibrous tissue. In the clinical cases these features were present in 24 instances on the right and in one on the left side of the ventricular septum, to an extent of more than 20% of the section in six patients, clinically positive for right ventricular dysplasia. On autoptic biopsy, fibro-adipose tissue was found in seven hearts, with different distribution on both ventricles, but to a maximum amount of 20% of the section. The right side of the ventricular septum was affected in five instances. Therefore in our material there is a quantitative difference on right ventricular biopsy with respect to fibro-adipose tissue in normal hearts and in cases with right ventricular dysplasia.

[The structural organization of the human myocardium: the interrelation between myocardial fibers and interstitial connective tissue]. / Organizzazione strutturale del miocardio umano: interrelazione fra fibre miocardiche e connettivo interstiziale.

The complex tridimensional structure of the human ventricular myocardium has rarely been studied in the past. In the normal heart, in the lapse of time of few weeks of the embryonic life, a radical transformation from a chaotic plexiform organization to a complex tridimensional structure occurs. From then on, the ulterior growth of the myocardial fibres will only be dimensional and quantitative, because the spatial geometry is to be considered definitive. The role of the interstitial connective tissue in following the development of the myocardium, possibly inducing or influencing it, is still unclear. We have performed an histologic study on serial sections of the ventricular mass of 7 human embryos and fetuses, from 5 to 20 weeks of gestational age. The sections have been evaluated for their morphologic characteristics as evidentiated by histochemical (PAS, trichrome, Gomori silver technique) and immunohistochemical (myosin, actin, desmin, myoglobin, vimentin, fibronectin, smooth muscle cell, endothelial factor VIII) stainings. The results show that myocardial growth is mantellar, proceeding from the epicardium toward the endocardium, with progressive structural organization in strata, variably related one to the other depending upon the considered site of the ventricular mass. The interstitium grows in parallel to the myocardial growth, beginning with a thin network surrounding each fibre that progressively in time is transformed in a complexly arranged and more densely packed structure. The collagen fibres appear initially at epicardial level, particularly around the coronary vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Occupational exposure to asbestos and urinary bladder cancer.

By the use of transmission electron microscopy (TEM) and energy dispersion spectrometry the amount (mean value mean = 191 +/- 94 fibers/mg of tissue) and the type (chrysotile and tremolite) of asbestos fibers have been determined in tissue samples of four bladder cancer patients affected by pulmonary asbestosis, working in the same plant producing asbestos-cement pipes and boards. Similar measurements were carried out on samples of bladder cancers of eight control patients not professionally exposed to asbestos. Only five of them also revealed chrysotile fibers (mean = 151 +/- 196 fibers/mg of tissue). The paucity of the study and control cases and the small quantitative difference between them regarding the presence of infraneoplastic asbestos fibers does not consent us to hypothesize a causal relationship between tumor and occupational exposure.

[Polycystic mesothelioma of the peritoneum. Description of 4 cases]. / Mesotelioma multicistico del peritoneo. Descrizione di quattro casi.

Cystic mesothelioma is a rare tumor of the peritoneal cavity arising from mesothelial cells. About 130 cases have been reported in the literature. The tumor is more frequent (85%) in adult women and rarely occurs in children. It is benign but recurrences are often described. The differential diagnosis with adenomatoid tumors, lymphangiomas, cystic malignant mesotheliomas and metastatic serous cystic tumors of the ovary is supported by immunohistochemistry. We describe four cases of cystic mesothelioma of the peritoneum; two of the cases occurred in pregnant women, one in a 45-year-old man and one in a 5-year-old boy. Asbestos exposure was not documented. The mesothelial origin of the neoplasms was supported by immunohistochemical analysis. Furthermore, tests for simian virus 40 (SV40 T antigen), to determine whether this virus was also present in the lesions, were negative.

[Gastric antral vascular ectasia (GAVE or watermelon stomach): a case report]. / Ectasia vascolare gastrica antrale (GAVE o watermelon stomach): descrizione di un caso.

Gastric antral vascular ectasia (GAVE), recently described in literature, is an important cause of gastric bleeding. A case of great gastrectasia with vascular ectasia in an elderly male patient is reported. The lesion was characterized by great linear and brush folds along the antrum and body of the stomach, Endoscopically, this folds seems like the watermelon streakings. It could be an acquired lesion probably linked to traumatism on gastric mucosa.