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.

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.

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.

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.

Malignant deciduoid mesothelioma of the pleura: report of two cases with long survival.

AIMS: To present two rare cases of malignant mesotheliomas with deciduoid features arising in the pleura, both with long survival. METHODS AND RESULTS: These two cases of deciduoid mesotheliomas were observed in adult patients (one 73-year-old male and one 23-year-old female). Only the male had a history of occupational asbestos exposure, whereas the woman had a history of familial mesothelioma. A deciduoid morphology was predominant and focal areas with tubular-papillary features were noted. The tumour cells were positive for cytokeratins, HMBE-1, calretinin, EMA and mitochondrion antibodies. The follow-up data did not suggest a particularly poor prognosis; the mean survival observed was 23 months (17 and 39 months, respectively). CONCLUSIONS: This deciduoid mesothelioma histological subtype does not appear to represent an unfavourable prognostic category.

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.

[The Ljubljana classification of epithelial hyperplastic laryngeal lesions: a morphometric evaluation of nuclear pleomorphism]. / La classificazione di Ljubljana delle lesioni iperplastiche dell'epitelio laringeo: valutazione morfometrica del pleomorfismo nucleare.

Epithelial hyperplastic laryngeal lesions (EHLL) are associated, with a varying degree of "epithelial risk"- to develop invasive carcinoma. Several classifications have been proposed but none has received a total agreement. The 1999 Ljubljana classification distinguished four grades: simple, abnormal and atypical hyperplasia and in situ carcinoma (ISC). The first two grades are considered benign lesions; the ISC is the malignant lesion, while the atypical hyperplasia is considered a "risky lesion". This is characterized by alterations of epithelial cells towards malignancy, but not to the extent to be found in carcinoma cells. Such characteristics refer to cytomorphological (e.g., nuclear hyperchromatism, nucleoli, increased nuclear/cytoplasmic ratio) and architectural (e.g. stratification, orientation, maturation) features. In the Ljubljana scheme, nuclear pleomorphism is one of the most important features. We wanted to improve the importance of nuclear pleomorphism in the basal cells layer in different classes of EHLL using morphometrical analysis. We studied 8 cases of simple hyperplasia, 10 of abnormal hyperplasia, 10 of atypical hyperplasia and 8 of ISC using the software SAM (Shape Analytical Morphometry). The results were submitted to univariate statistical analysis. Nuclear dimensions (maximum diameter, perimeter and area) showed a progressive increase from simple to atypical hyperplasias to ISC, while abnormal hyperplasia showed the lowest values. On the contrary, analytical parameters related to nuclear contour irregularities and asymmetries showed their highest values in abnormal hyperplasia nuclei. There were no significant differences between atypical hyperplasia and ISC, while it was possible to differentiate abnormal hyperplasia from the others. In conclusion basal nuclei of atypical hyperplasia and ISC are similar so that other cytological and morphological architectural parameters are necessary to distinguish the two lesions. Abnormal hyperplasia seems to be the biological category of 'proliferative " benign laryngeal epithelium; simple hyperplasia refers to "stable" - irritative epithelium.

[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.

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.

Malignant fibrous histiocytoma of the larynx after radiotherapy for squamous cell carcinoma.

A few cases of malignant fibrous histiocytoma (MFH) of the larynx have been reported to date. All ages may be affected, but the tumor is more prevalent in the sixth and seventh decade of life. We describe a case of MFH in a 71-year-old Italian man who 8 years before underwent a right cordectomy and radiotherapy for squamous cell carcinoma. Recurrent tumor was found to be MFH. The clinico-pathological features of this tumor are presented and the possible relationship between radiotherapy and MFH discussed. The neoplasm was characterized by spindle-shaped atypical cells arranged in a diffuse storiform pattern. Mitoses were prominent, numerous, and often atypical. Immunohistochemically, neoplastic cells were strongly positive for vimentin and alpha1-antichymotrypsin but were negative for cytokeratins and S-100 protein. These findings confirmed the diagnosis and excluded possible sarcomatoid carcinoma, inflammatory pseudotumor, and a new carcinosarcoma. The risk of sarcoma after radiotherapy for squamous cell carcinoma in the larynx is very low when considering the frequent use of radiotherapy, but long follow-ups are required.

[Oncocytic meningioma. Case report]. / Meningioma oncocitario. Descrizione di un caso.

Among the histological variants of meningiomas the oncocytic subtype is rarely observed. Up-today, only six cases of oncocytic meningioma are described. This subtype of meningiomas shows an aggressive behavior and recurrences are more frequent. We describe a case of oncocytic meningioma in a 78-years-old woman. The patient had a history of breast cancer diagnosed 9 years before the brain biopsy; bilateral mastectomy and adjuvant chemotherapy was performed. She had a right frontal tumour measuring 3 cm in diameter. The patient is alive and well eleven months after surgery. The tumour was composed by large polygonal neoplastic cells with finely granular eosinophilic cytoplasm. Neoplastic cells were arranged in sheets and nests delimited by thin fibrous septa rich in vessels. Psammomatous bodies were also present. Mitoses were rare and necrosis was absent. Oncocytic differentiation was demonstrated by conventional histology and immunohistochemistry. Immunohistochemistry revealed a strong and diffuse positivity for antimitochondrial antiserum, vimentin and EMA; a focal reactivity for cytokeratin was observed. The rarity of oncocytic meningiomas is underlined with only six cases described in the world literature. The immunophenotypic profile and the differential diagnosis of the neoplasm is discussed and the concept of oncocytic meningioma as a distinct entity of tumour is emphasized.

[Atypical meningioma: morphometric analysis of nuclear pleomorphism]. / Meningioma Atipico: un'analisi morfometrica del polimorfismo nucleare.

The revised edition of the WHO classification of brain tumours now includes the "atypical" meningioma (grade II) which should be placed between the common type (grade I) and anaplastic type (grade III) according to histomorphological features and prognosis. However, diagnostic criteria for atypical meningioma are vague and the significance of brain invasion in the determination of malignancy is controversial. Nuclear pleomorphism and mitoses are usually considered the most important parameters to distinguish atypical and malignant meningiomas. According to WHO classification we selected eight cases of meningioma diagnosed as atypical (3 cases) and malignant (5 cases). All the tumours were supratentorially located. Nine cases of benign meningiomas were also studied as a control group. Morphometrical analysis was carried out by S.A.M. (Shape Analytical Morphometry) system. S.A.M. 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 and the numerical level. The results, statistically evaluated, show that nuclear pleomorphism is not a satisfactory criterion, if used alone, to distinguish atypical from malignant meningioma (Discriminant Analysis: 19% of minimum error).

[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.

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.

Malignant large cell calcifying Sertoli cell tumor of the testis (LCCSCTT). Report of a case in an elderly man and review of the literature.

Malignant Large Cell Calcifying Sertoli Cell Tumor of the Testis (LCCSCTT) is a rare histological variant of sex cordstromal tumors. It usually arises in young males, sometimes is associated with endocrine abnormalities and has a benign course. It is exceptional in elderly men and the outcome is rarely fatal. We report a case of LCCSCTT in a 73 year-old man with fatal outcome. The tumor involved the right testis and several areas of the tunica albuginea were grossly invaded. Serum levels of HCG, LH and testosterone were normal. Lymphoangiography performed after orchiectomy showed an involvement of the iliac and preaortic lymph nodes. X-ray of the chest showed no lung metastases. A thorough study of the light microscopic, immunohistochemical and ultrastructural appearances was performed. Immunohistochemistry revealed positivity to vimentin, S-100 and NSE. Our observations confirm the previous findings concerning malignant LCCSCTT and point out the histogenesis of the tumor from Sertoli cells.

[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.

The axonally secreted serine proteinase inhibitor, neuroserpin, inhibits plasminogen activators and plasmin but not thrombin.

Neuroserpin is an axonally secreted serine proteinase inhibitor that is expressed in neurons during embryogenesis and in the adult nervous system. To identify target proteinases, we used a eucaryotic expression system based on the mouse myeloma cell line J558L and vectors including a promoter from an Ig-kappa-variable region, an Ig-kappa enhancer, and the exon encoding the Ig-kappa constant region (C kappa) and produced recombinant neuroserpin as a wild-type protein or as a fusion protein with C kappa. We investigated the capability of recombinant neuroserpin to form SDS-stable complexes with, and to reduce the amidolytic activity of, a variety of serine proteinases in vitro. Consistent with its primary structure at the reactive site, neuroserpin exhibited inhibitory activity against trypsin-like proteinases. Although neuroserpin bound and inactivated plasminogen activators and plasmin, no interaction was observed with thrombin. A reactive site mutant of neuroserpin neither formed complexes with nor inhibited the amidolytic activity of any of the tested proteinases. Kinetic analysis of the inhibitory activity revealed neuroserpin to be a slow binding inhibitor of plasminogen activators and plasmin. Thus, we postulate that neuroserpin could represent a regulatory element of extracellular proteolytic events in the nervous system mediated by plasminogen activators or plasmin.

[Malignant mesothelioma of the pleura. Morphometric study]. / Il mesotelioma maligno della pleura. Studio morfometrico.

Malignant mesothelioma is difficult to distinguish from other pleural malignancies and also from benign mesothelial lesions. A morphometric study has been performed to distinguish between them using quantitative size and shape parameters. Seven cases of malignant mesothelioma, 5 cases of pleural metastatic adenocarcinoma and 4 cases of benign mesothelial lesions were selected and subjected to S.A.M. (Shape Analytical Morphometry). The results, statistically evaluated, showed that morphometric parameters can be proposed for diagnostic purposes being useful in the discrimination among the three populations. In fact, multivariate discriminant analysis (MDA) of the quantitative parameters obtained by morphometrical study distinguished the three groups of lesions with only 2% of error between BML/MM, 7% of error between BML/MA and 25% between MM/MA.